2024/03/21 更新

写真a

イナバ ヒロアキ
稲葉 裕明
INABA Hiroaki
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士(歯学)

研究キーワード

  • apoptosis

  • 細胞周期

  • P. gulae

経歴

  • 岡山大学大学院 医歯薬学総合研究科 准教授

    2016年 - 現在

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  • 岡山大学病院 講師

    2015年 - 2016年

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  • 朝日大学歯学部 講師

    2014年 - 2015年

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  • 大阪大学大学院歯学研究科 助教

    2009年 - 2014年

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  • 米国フロリダ大学歯学部 博士研究員

    2007年 - 2009年

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  • 大阪大学   Graduate School of Dentistry

    2007年

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  • 大阪大学   Graduate School of Dentistry

    2002年 - 2006年

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▼全件表示

 

論文

  • Investigation of periodontal disease development and Porphyromonas gulae FimA genotype distribution in small dogs. 国際誌

    Junya Yasuda, Hidemi Yasuda, Ryota Nomura, Saaya Matayoshi, Hiroaki Inaba, Enrique Gongora, Naoki Iwashita, So Shirahata, Noriyuki Kaji, Tatsuya Akitomo, Chieko Mitsuhata, Jumpei Uchiyama, Tomoki Fukuyama, Michiyo Matsumoto-Nakano, Kazuhiko Nakano, Masaru Murakami

    Scientific reports   14 ( 1 )   5360 - 5360   2024年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In dogs, Porphyromonas gulae is a major periodontal pathogen with 41-kDa proteins polymerizing to form a filamentous structure called fimbriae or pili, termed FimA. FimA is classified into three genotypes: A, B, and C, and there are combinations of types A, B, C, A/B, A/C, B/C, and A/B/C. Periodontal disease is the most common oral disease in small dogs, but the periodontal disease status and P. gulae colonization at each dog age and breed remain unclear. In this study, we stratified 665 small dogs and analyzed the periodontal status and distribution of P. gulae with each FimA genotype. Dogs with periodontal disease and FimA genotype tended to increase with age. The dogs with at least one FimA genotype had significantly more severe periodontal disease compared with P. gulae-negative dogs (P < 0.01). Additionally, periodontal status was significantly associated with specific FimA genotype distribution in Toy Poodles and Chihuahuas (P < 0.05), whereas there was no such association in Dachshunds. These results suggest that the onset of periodontal disease and P. gulae colonization are related and progress with age. The relationship between periodontal disease and FimA genotype may differ depending on the dog breeds.

    DOI: 10.1038/s41598-024-55842-8

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  • Transcriptomic analysis of Porphyromonas gingivalis-infected head and neck cancer cells: Identification of PLAU as a candidate prognostic biomarker. 国際誌

    Masakazu Hamada, Hiroaki Inaba, Kyoko Nishiyama, Sho Yoshida, Yoshiaki Yura, Michiyo Matsumoto-Nakano, Narikazu Uzawa

    Journal of cellular and molecular medicine   28 ( 4 )   2024年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Periodontal disease is a risk factor for head and neck squamous cell carcinoma (HNSCC), and Porphyromonas gingivalis, a major periodontal pathogen, has been identified as a specific and potentially independent microbial factor that increases the risk of cancer mortality. Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. When P. gingivalis was cultured with HNSCC cells, it efficiently adhered to these cells and enhanced their invasive ability. A transcriptome analysis of P. gingivalis -infected HNSCC cells showed that genes related to migration, including CCL20, CITED2, CTGF, C8orf44-SGK3, DUSP10, EGR3, FUZ, HBEGF, IL1B, IL24, JUN, PLAU, PTGS2, P2RY1, SEMA7A, SGK1 and SIX2, were highly up- or down-regulated. The expression of up-regulated genes was examined using the expression data of HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database, and the expression of 5 genes, including PLAU, was found to be higher in cancer tissue than in solid normal tissue. An analysis of protein-protein interactions revealed that these 5 genes formed a dense network. A Cox regression analysis showed that high PLAU expression levels were associated with a poor prognosis in patients with TCGA-HNSCC. Furthermore, the prognostic impact correlated with tumour size and the presence or absence of lymph node metastasis. Collectively, these results suggest the potential of PLAU as a molecular prognostic marker in HNSCC patients. Further in vivo and in vitro studies are needed to verify the findings of this study.

    DOI: 10.1111/jcmm.18167

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  • Potential role of the intratumoral microbiota in prognosis of head and neck cancer 査読

    Masakazu Hamada, Hiroaki Inaba, Kyoko Nishiyama, Sho Yoshida, Yoshiaki Yura, Michiyo Matsumo-to-Nakano, Narikazu Uzawa

    International Journal of Molecular Sciences   2023年10月

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  • Porphyromonas gulae線毛遺伝子多型とバイオフィルムへの影響

    吉田 翔, 稲葉 裕明, 野村 良太, 仲野 和彦, 仲野 道代

    小児歯科学雑誌   61 ( 大会抄録号 )   231 - 231   2023年4月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Possible association of fimA genotype of Porphyromonas gulae with the severity of periodontal disease and the number of permanent teeth in dogs 査読

    So Shirahata, Naoki Iwashita, Rie Sasaki, Ryota Nomura, Masaru Murakami, Junya Yasuda, Hidemi Yasuda, Kuniyasu Nakajima, Hiroaki Inaba, Michiyo Matsumoto-Nakano, Kazuhiko Nakano, Jumpei Uchiyama and Tomoki Fukuyama

    Frontier in veterinary   2023年1月

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    記述言語:英語  

  • Possible association of fimA genotype of Porphyromonas gulae with the severity of periodontal disease and the number of permanent teeth in dogs 査読 国際誌

    Frontiers in Veterinary Science   10   1022838 - 1022838   2023年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fvets.2023.1022838

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  • Characterization of protease from animal periodontal pathogen Porphyromonas gulae 査読

    Alam Saki Urmi, Hiroaki Inaba, Sho Yoshida, Ryota Nomura, Kazuhiko Nakano, Michiyo 4 Matsumoto-Nakano

    Japanese Journal of Veterinary Research   2022年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Green tea catechins inhibit Porphyromonas gulae LPS-induced inflammatory responses in human gingival epithelial cells 査読 国際誌

    Sho Yoshida, Hiroaki Inaba, Ryota Nomura, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    Journal of oral biosciences   2022年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To determine the anti-inflammatory effects of green tea catechins in immortalized human gingival epithelial cells (Ca9-22) stimulated with Porphyromonas gulae lipopolysaccharide (LPS). METHODS: Ca9-22 cells were incubated with P. gulae LPS (10 μg/ml) with or without green tea catechins, epigallocatechin-3-gallate (EGCg), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (each at 50 μM), for 6 or 24 hours. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay were used to determine the induction of cyclooxygenase 2 (COX2), tumor necrosis factor alpha (TNF-ɑ), interleukin 6 (IL-6), and IL-8. Furthermore, the expression of toll-like receptors (TLRs) 2 and 4 was examined using real-time PCR and western blotting analysis, and phosphorylation of the p38 and ERK1/2 was examined using western blotting analysis. RESULTS: At the mRNA and protein levels, EGCg, EGC, ECG, and EC were found to significantly inhibit COX2, TNF-ɑ, IL-6, and IL-8. Furthermore, the levels of ERK1/2 and p38 phosphorylation induced by P. gulae LPS were decreased following the addition of each of the catechins, as well as TLR2 and 4 mRNA and protein. CONCLUSIONS: These findings indicate that green tea catechins are potent inhibitors of inflammatory responses induced by P. gulae LPS, and may also be useful for prevention and/or attenuation of periodontitis.

    DOI: 10.1016/j.job.2022.05.006

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  • Characterization of protease from animal periodontal pathogen Porphyromonas gulae 査読

    Alam Saki Urmi, Hiroaki Inaba, Sho Yoshida, Ryota Nomura, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    Japanese Journal of Veterinary Research   2022年

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    担当区分:責任著者   記述言語:英語  

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  • Porphyromonas gulae LPS誘発炎症反応における緑茶ポリフェノールの抗炎症作用(Green tea-derived polyphenols inhibited inflammatory responses stimulated with P.gulae LPS)

    稲葉 裕明, 吉田 翔, 仲野 道代, 野村 良太, 仲野 和彦

    Journal of Oral Biosciences Supplement   2021   217 - 217   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Prognostic association of starvation-induced gene expression in head and neck cancer. 査読 国際誌

    Masakazu Hamada, Hiroaki Inaba, Kyoko Nishiyama, Sho Yoshida, Yoshiaki Yura, Michiyo Matsumoto-Nakano, Narikazu Uzawa

    Scientific reports   11 ( 1 )   19130 - 19130   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion. To investigate the dynamics of expression of genes, including ARGs, head and neck squamous cell carcinoma (HNSCC) cells were placed under serum-free conditions to induce growth retardation and autophagy, and these starved cells were subjected to transcriptome analysis. Among the 21 starvation-induced genes (SIGs) located in the autophagy, cell proliferation, and survival signaling pathways, we identified SIGs that showed prominent up-regulation or down-regulation in vitro. These included AGR2, BST2, CALR, CD22, DDIT3, FOXA2, HSPA5, PIWIL4, PYCR1, SGK3, and TRIB3. The Cancer Genome Atlas (TCGA) database of HNSCC patients was used to examine the expression of up-regulated genes, and CALR, HSPA5, and TRIB3 were found to be highly expressed relative to solid normal tissue in cancer and the survival rate was reduced in patients with high expression. Protein-protein interaction analysis demonstrated the formation of a dense network of these genes. Cox regression analysis revealed that high expression of CALR, HSPA5, and TRIB3 was associated with poor prognosis in patients with TCGA-HNSCC. Therefore, these SIGs up-regulated under serum starvation may be molecular prognostic markers in HNSCC patients.

    DOI: 10.1038/s41598-021-98544-1

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  • Efficacy of FimA antibody and clindamycin in silkworm larvae stimulated with Porphyromonas gulae. 査読 国際誌

    Sho Yoshida, Hiroaki Inaba, Ryota Nomura, Masaru Murakami, Hidemi Yasuda, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    Journal of Oral Microbiology   13 ( 1 )   1914499 - 1914499   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: Porphyromonas gulae, a major periodontal pathogen in animals, possesses fimbriae that have been classified into three genotypes (A, B, C) based on the diversity of fimA genes encoding fimbrillin protein (FimA). P. gulae strains with type C fimbriae were previously shown to be more virulent than other types. In this study, we further examined the host toxicity mediated by P. gulae fimbriae by constructing recombinant FimA (rFimA) expression vectors for each genotype and raised antibodies to the purified proteins. Methods and Results: All larvae died within 204 h following infection with P. gulae type C at the low-dose infection, whereas type A and B did not. Among fimA types, the survival rates of the larvae injected with rFimA type C were remarkably decreased, while the survival rates of the larvae injected with rFimA type A and type B were greater than 50%. Clindamycin treatment inhibited the growth of type C strains in a dose-dependent manner, resulting in an increased rate of silkworm survival. Finally, type C rFimA-specific antiserum prolonged the survival of silkworm larvae stimulated by infection with P. gulae type C strain or injection of rFimA type C protein. Conclusion: These results suggested that type C fimbriae have high potential for enhancement of bacterial pathogenesis, and that both clindamycin and anti-type C rFimA-specific antibodies are potent inhibitors of type C fimbriae-induced toxicity. This is the first report to establish a silkworm infection model using P. gulae for toxicity assessment.

    DOI: 10.1080/20002297.2021.1914499

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  • Roles of Porphyromonas gulae proteases in bacterial and host cell biology. 査読 国際誌

    Alam Saki Urmi, Hiroaki Inaba, Ryota Nomura, Sho Yoshida, Naoya Ohara, Fumitoshi Asai, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    Cellular microbiology   23 ( 8 )   e13312   2021年1月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Porphyromonas gulae, an animal-derived periodontal pathogen, expresses several virulence factors, including fimbria, lipopolysaccharide (LPS), and proteases. We previously reported that its invasive efficiency was dependent on fimbriae types. In addition, P. gulae LPS increased inflammatory responses via toll-like receptors. The present study was conducted to investigate the involvement of P. gulae proteases in bacterial and host cell biology. P. gulae strains showed an ability to agglutinate mouse erythrocytes and also demonstrated coaggregation with Actinomyces viscosus, while the protease inhibitors antipain, PMSF, TLCK, and leupeptin diminished P. gulae proteolytic activity, resulting in inhibition of hemagglutination and coaggregation with A. viscosus. In addition, specific proteinase inhibitors were found to reduce bacterial cell growth. P. gulae inhibited Ca9-22 cell proliferation in a multiplicity of infection- and time-dependent manner. Additionally, P. gulae-induced decreases in cell contact and adhesion-related proteins were accompanied by a marked change in cell morphology from well spread to rounded. In contrast, inhibition of protease activity prevented degradation of proteins, such as E-cadherin, β-catenin, and focal adhesion kinase, and also blocked inhibition of cell proliferation. Together, these results indicate suppression of the amount of human proteins, such as γ-globulin, fibrinogen and fibronectin, by P. gulae proteases, suggesting that a novel protease complex contributes to bacterial virulence. This article is protected by copyright. All rights reserved.

    DOI: 10.1111/cmi.13312

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  • Porphyromonas gulae lipopolysaccharide elicits inflammatory responses through toll-like receptor 2 and 4 in human gingivalis epithelial cells. 査読 国際誌

    Hiroaki Inaba, Sho Yoshida, Ryota Nomura, Yukio Kato, Fumitoshi Asai, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    Cellular microbiology   22 ( 12 )   e13254   2020年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Porphyromonas gulae, a Gram-negative black-pigmented anaerobe, has been associated with periodontal disease in companion animals and its virulence has been attributed to various factors, including lipopolysaccharide (LPS), protease and fimbriae. Toll-like receptors (TLRs) recognise pathogen-associated molecular patterns, such as peptidoglycan, lipids, lipoproteins, nucleic acid and LPS. Following P. gulae infection, some inflammatory responses are dependent on both TLR2 and TLR4. In addition, a recent clinical study revealed that acute and persistent inflammatory responses enhance the expressions of TLR2 and TLR4 in the oral cavity. In this study, we investigated the interaction between P. gulae LPS and human gingivalis epithelial cells (Ca9-22 cells). P. gulae LPS was found to increase TLR2 and TLR4 mRNA expressions and protein productions, and enhanced inflammatory responses, such as COX2 , TNF-ɑ, IL-6 and IL-8. Stimulated Ca9-22 cells exhibited phosphorylation of ERK1/2 and p38, and their inhibitors diminished inflammatory responses, while knockdown of the TLR2 and/or TLR4 genes with small interfering RNA (siRNA) prevented inflammatory responses. Moreover, p38 and ERK1/2 phosphorylation was decreased in TLR2 and TLR4 gene knockdown cells. These findings suggest that P. gulae LPS activates p38 and ERK1/2 via TLR2 and TLR4, leading to inflammatory responses in human gingival epithelial cells.

    DOI: 10.1111/cmi.13254

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  • Identification and functional analysis of glutamine transporter in Streptococcus mutans. 国際誌

    Yuko Morikawa, Setsuyo Morimoto, Eri Yoshida, Shuhei Naka, Hiroaki Inaba, Michiyo Matsumoto-Nakano

    Journal of oral microbiology   12 ( 1 )   1797320 - 1797320   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Streptococcus mutans, a biofilm-forming bacterium, possesses several transporters that function as import/export molecules. Among them, the PII protein family is composed of members that regulate glutamine synthesis in bacterial species. Objective: In this study, we characterized the function of the glutamine transporter in S. mutans MT8148. Methods: The SMU.732 gene, corresponding to glnP in S. mutans, is homologous to the glutamine transporter gene in Bacillus subtilis. We constructed a glnP-inactivated mutant strain (GEMR) and a complement strain (comp-GEMR) and evaluated their biological functions. Results: Growth of GEMR was similar in the presence and absence of glutamine, whereas the growth rates of MT8148 and comp-GEMR were significantly lower in the presence of glutamine as compared to its absence. Furthermore, biofilms formed by MT8148 and comp-GEMR were significantly thicker than that formed by GEMR, while the GEMR strain showed a significantly lower survival rate in an acidic environment than the other strains. Addition of n-phenyl-2-naphthylamine, used to label of the membrane, led to increased fluorescence intensity of MT8148 and GEMR, albeit that was significantly lower in the latter. Conclusions: These results suggest that glnP is associated with glutamine transport in S. mutans, especially the import of glutamine involved in biofilm formation.

    DOI: 10.1080/20002297.2020.1797320

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  • Author Correction: Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha. 国際誌

    Ryota Nomura, Hiroaki Inaba, Hidemi Yasuda, Mitsuyuki Shirai, Yukio Kato, Masaru Murakami, Naoki Iwashita, So Shirahata, Sho Yoshida, Saaya Matayoshi, Junya Yasuda, Nobuaki Arai, Fumitoshi Asai, Michiyo Matsumoto-Nakano, Kazuhiko Nakano

    Scientific reports   10 ( 1 )   7295 - 7295   2020年4月

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    記述言語:英語  

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    DOI: 10.1038/s41598-020-63861-4

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  • Porphyromonas gulaeプロテアーゼによる歯肉上皮細胞傷害能の評価

    吉田 翔, 稲葉 裕明, Alam Urmi Saki, 野村 良太, 仲野 和彦, 仲野 道代

    小児歯科学雑誌   58 ( 大会抄録(誌上開催)号 )   106 - 106   2020年4月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • The role of Porphyromonas gulae protease on bacterial growth and hemagglutination

    Urmi Saki Alam, 稲葉裕明, 吉田翔, 野村良太, 仲野和彦, 仲野道代

    58 ( 大会抄録(誌上開催)号 )   116 - 116   2020年4月

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    記述言語:英語  

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  • Inhibitory effect of a mouth rinse formulated with chlorhexidine gluconate, ethanol, and green tea extract against major oral bacterial species.

    Ryota Nomura, Hiroaki Inaba, Saaya Matayoshi, Sho Yoshida, Yuki Matsumi, Michiyo Matsumoto-Nakano, Kazuhiko Nakano

    Journal of oral science   62 ( 2 )   206 - 211   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mouth rinses are a useful supplementary tool for the prevention of oral infectious diseases. Although the antimicrobial effects of mouth rinses have been investigated, there are few studies focusing on the comparison of the effects among various oral bacterial species. In the present study, the inhibitory effect of a commercial mouth rinse, "ConCoolF," and each of its major components, chlorhexidine gluconate, ethanol, and green tea extract, on multiple species of oral bacteria were investigated. Inhibition of bacterial growth was observed in all cariogenic streptococcal species with different genera, serotypes, and strains isolated from different countries when either the complete mouth rinse or chlorhexidine gluconate were used. However, no growth inhibition was observed when the bacteria were exposed to ethanol or green tea extract. Interestingly, growth inhibition was greatly reduced in non-cariogenic streptococci compared with cariogenic streptococci. In addition, both the mouth rinse and chlorhexidine gluconate inhibited the biofilms formed by both Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis), among which the inhibitory effect against S. mutans was higher than that against P. gingivalis. These results suggest that a mouth rinse containing chlorhexidine gluconate, ethanol, and green tea extract, or chlorhexidine gluconate alone, exhibits antimicrobial activity against several oral bacteria species, having greater activity against pathogenic bacteria.

    DOI: 10.2334/josnusd.18-0483

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  • Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha. 国際誌

    Ryota Nomura, Hiroaki Inaba, Hidemi Yasuda, Mitsuyuki Shirai, Yukio Kato, Masaru Murakami, Naoki Iwashita, So Shirahata, Sho Yoshida, Saaya Matayoshi, Junya Yasuda, Nobuaki Arai, Fumitoshi Asai, Michiyo Matsumoto-Nakano, Kazuhiko Nakano

    Scientific reports   10 ( 1 )   3113 - 3113   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and IFN-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of FimA genotypes in oral specimens from treated dogs. These results suggest that a combination of clindamycin and IFN-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.

    DOI: 10.1038/s41598-020-59730-9

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  • Porphyromonas gulae由来のプロテアーゼ活性の評価

    吉田 翔, 稲葉 裕明, Alam Urmi Saki, 仲野 道代, 野村 良太, 仲野 和彦

    小児歯科学雑誌   58 ( 地方会抄録号 )   58 - 58   2020年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Characterization of bacterial proteases from Porphyromonas gulae strains.

    Urmi Saki Alam, Hiroaki Inaba, Sho Yoshida, Ryota Nomura, Kazuhiko Nakano, Michiyo Matsumoto-Nakano

    日本細菌学会   75 ( 1 )   88 - 88   2020年1月

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    記述言語:英語  

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  • 動物由来歯周病原菌のプロテアーゼ活性の評価

    吉田 翔, 稲葉 裕明, Alam Urmi Saki, 野村 良太, 仲野 和彦, 仲野 道代

    岡山歯学会雑誌   38 ( 2 )   90 - 91   2019年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • コンクールFとその構成成分における口腔細菌種への増殖抑制効果の検討

    又吉 紗綾, 野村 良太, 稲葉 裕明, 吉田 翔, 松三 友紀, 仲野 道代, 仲野 和彦

    小児歯科学雑誌   57 ( 2 )   188 - 188   2019年5月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Adhesion and invasion of gingival epithelial cells by Porphyromonas gulae. 査読

    Inaba H, Nomura R, Kato Y, Takeuchi H, Amano A, Asai F, Nakano K, Lamont RJ, Matsumoto-Nakano M

    PLOS ONE   2019年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Identification and molecular characterization of Porphyromonas gulae fimA types among cat isolates. 国際誌

    Naoki Iwashita, Ryota Nomura, Mitsuyuki Shirai, Yukio Kato, Masaru Murakami, Saaya Matayoshi, Tamami Kadota, So Shirahata, Leo Ohzeki, Nobuaki Arai, Junya Yasuda, Hidemi Yasuda, Hiroaki Inaba, Michiyo Matsumoto-Nakano, Kazuhiko Nakano, Fumitoshi Asai

    Veterinary microbiology   229   100 - 109   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Porphyromonas gulae, a Gram-negative black-pigmented anaerobe, is one of several major periodontal pathogens of animals. P. gulae isolates from dogs have been classified into three genotypes based on a 41-kDa filamentous appendage (FimA) on the cell surface, which is closely related to virulence in periodontal disease. However, other specific bacterial virulence factors contributing to the aggravation of periodontal disease in cats remain elusive. In the present study, we assessed FimA diversity in P. gulae isolates from cats and examined whether this diversity influenced periodontal condition. The putative amino acid sequences of FimA from 15 P. gulae isolates from 13 cats were classified into three genotypes (types A, B, and C), which showed 95-100% identity and similarity to the fimA types in dogs. The type C isolate showed greater adhesion and invasion properties in periodontal ligament fibroblasts as well as stronger inhibition of scratch closure of the cells compared with type A and B isolates. Next, a PCR-based method for identification of fimA genotype was developed and used to analyze 99 oral swab specimens from cats. High fimA type A detection rates were observed regardless of the periodontal condition, whereas types B and C were frequently detected from subjects with moderate and severe periodontitis, respectively. These results suggest that P. gulae isolates from cats can be classified into three types based on fimA genotype, which may be closely related to virulence in periodontitis.

    DOI: 10.1016/j.vetmic.2018.12.018

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  • 侵襲性歯周炎により乳歯の脱落を来した小児の1例

    仲 周平, 田畑 佳子, 稲葉 裕明, 仲野 道代

    小児歯科学雑誌   57 ( 1 )   135 - 135   2019年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • 生体機能性材料S-PRGフィラーの口腔バイオフィルム構造決定因子に対する影響

    高島 由紀子, 森川 優子, 森本 節代, 仲 周平, 稲葉 裕明, 仲野 道代

    小児歯科学雑誌   57 ( 1 )   127 - 127   2019年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Porphyromonas gulae線毛の遺伝子多型と歯肉上皮細胞への侵入能

    稲葉 裕明, 吉田 翔, 仲野 道代, 野村 良太, 仲野 和彦

    Journal of Oral Biosciences Supplement   2018   493 - 493   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients 査読

    Taro Misaki, Shuhei Naka, Kaoruko Wato, Rina Hatakeyama, Yasuyuki Nagasawa, Seigo Ito, Hiroaki Inaba, Ryota Nomura, Michiyo Matsumoto-Nakano, Kazuhiko Nakano

    Nephron   139 ( 2 )   143 - 149   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    Background: Periodontitis-related pathogens, such as Campylobacter or Treponema species, have recently been shown to be associated with immunoglobulin A nephropathy (IgAN). Some strains of Streptococcus mutans, a major pathogen of dental caries, harbour the cnm gene that encodes a collagen-binding protein (Cnm). This has also been demonstrated to be associated with urinary protein levels in IgAN patients. Objectives: The purpose of the present study was to analyse the association of IgAN with C. rectus, Treponema denticola and cnm-positive S. mutans in the oral cavity of humans. Methods: The presence of C. rectus, T. denticola and cnm-positive S. mutans strains in saliva samples of 117 IgAN patients and 56 healthy controls was evaluated by PCR, and the subjects' clinical parameters were analysed. Results: C. rectus was significantly more prevalent in the IgAN group than in the control group (p &lt
    0.05). The C. rectus-positive group was significantly associated with proteinuria in the IgAN group (p &lt
    0.05). In addition, the C. rectus-positive and cnm-positive S. mutans group was shown to be more closely associated with urinary protein levels than the other groups (p &lt
    0.0083). Conclusion: Our results suggest that harbouring C. rectus in the oral cavity could be associated with proteinuria in IgAN patients.

    DOI: 10.1159/000487103

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  • Cell cycle arrest and apoptosis induced by Porphyromonas gingivalis require Jun N-terminal protein kinase- and p53- mediated p38 activation in human trophoblasts 査読

    Hiroaki Inaba, Atsuo Amano, Richard J. Lamont, Yukitaka Murakami, Michiyo Matsumoto-Nakano

    Infection and Immunity   86 ( 4 )   2018年4月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Microbiology  

    Porphyromonas gingivalis, a periodontal pathogen, has been implicated as a causative agent of preterm delivery of low-birth-weight infants. We previously reported that P. gingivalis activated cellular DNA damage signaling pathways and ERK1/2 that lead to G1 arrest and apoptosis in extravillous trophoblast cells (HTR-8 cells) derived from the human placenta. In the present study, we further examined alternative signaling pathways mediating cellular damage caused by P. gingivalis. P. gingivalis infection of HTR-8 cells induced phosphorylation of p38 and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both G1 arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was phosphorylated through both p38 and JNK, and knockdown of HSP27 with small interfering RNA (siRNA) prevented both G1 arrest and apoptosis. Furthermore, regulation of G1 arrest and apoptosis was associated with p21 expression. HTR-8 cells infected with P. gingivalis exhibited upregulation of p21, which was regulated by p53 and HSP27. These results suggest that P. gingivalis induces G1 arrest and apoptosis via novel molecular pathways that involve p38 and JNK with its downstream effectors in human trophoblasts.

    DOI: 10.1128/IAI.00923-17

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  • Porphyromonas gulae LPSによる歯肉上皮細胞の炎症性反応の評価

    吉田 翔, 稲葉 裕明, Alam Urmi Saki, 野村 良太, 仲野 和彦, 仲野 道代

    小児歯科学雑誌   56 ( 2 )   195 - 195   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Porphyromonas gulaeが産生するプロテアーゼに関する検討(Examination of Porphyromonas gulae protease)

    Alam Urmi Saki, 吉田 翔, 稲葉 裕明, 野村 良太, 仲野 和彦, 仲野 道代

    小児歯科学雑誌   56 ( 2 )   196 - 196   2018年4月

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    記述言語:英語   出版者・発行元:(公社)日本小児歯科学会  

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  • 扁桃におけるコラーゲン結合タンパク陽性Streptococcus mutansの存在はIgA腎症の発症および蛋白尿と関連する

    伊藤 誓悟, 三崎 太郎, 野村 良太, 大継 將寿, 山形 瑛, 松原 秀史, 今給黎 敏彦, 大島 直紀, 仲 周平, 和唐 薫子, 畠山 理那, 長澤 康行, 稲葉 裕明, 仲野 道代, 仲野 和彦, 熊谷 裕生

    日本腎臓学会誌   60 ( 3 )   407 - 407   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本腎臓学会  

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  • Porphyromonas gulaeの歯肉上皮細胞株への付着・侵入機構の解析

    稲葉 裕明, 野村 良太, 仲野 和彦, 仲野 道代

    日本細菌学雑誌   73 ( 1 )   115 - 115   2018年2月

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    記述言語:日本語   出版者・発行元:日本細菌学会  

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  • カイコ感染モデルを用いたPorphyromonas gulae FimAの病原性解析

    吉田 翔, 稲葉 裕明, 仲野 道代, 野村 良太, 仲野 和彦

    Journal of Oral Biosciences Supplement   2017   337 - 337   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 歯周病菌Porphyromonas gulae線毛遺伝子多型とヒト歯肉上皮細胞への付着・侵入能の解析

    吉田 翔, 稲葉 裕明, 野村 良太, 仲野 和彦, 仲野 道代

    小児歯科学雑誌   55 ( 2 )   314 - 314   2017年4月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • 犬における歯周病進行と年齢・犬種およびPorphylomonas gulae菌保有の関連性

    荒井 延明, 安田 隼也, 津村 はな, 稲葉 裕明, 仲野 道代, 野村 良太, 仲野 和彦, 白井 明志, 浅井 史敏

    動物臨床医学会年次大会プロシーディング   37回 ( 3 )   25 - 28   2016年11月

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    記述言語:日本語   出版者・発行元:動物臨床医学会  

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  • Apple-and Hop-Polyphenols Inhibit Porphyromonas gingivalis-Mediated Precursor of Matrix Metalloproteinase-9 Activation and Invasion of Oral Squamous Cell Carcinoma Cells 査読

    Hiroaki Inaba, Motoyuki Tagashira, Tomomasa Kanda, Yukitaka Murakami, Atsuo Amano, Michiyo Matsumoto-Nakano

    JOURNAL OF PERIODONTOLOGY   87 ( 9 )   1103 - 1111   2016年9月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis is markedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinase-activated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined.
    Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis.
    Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not.
    Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.

    DOI: 10.1902/jop.2016.160047

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  • P.gingivalis感染によるp38/JNKを介したヒト胎盤栄養膜細胞のアポトーシス誘導

    稲葉 裕明, 天野 敦雄, 仲野 道代, Lamont Richard J.

    Journal of Oral Biosciences Supplement   2016   545 - 545   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Involvement of protease-activated receptor 4 in over-expression of matrix metalloproteinase 9 induced by Porphyromonas gingivalis 査読

    Hiroaki Inaba, Atsuo Amano, Richard J. Lamont, Yukitaka Murakami

    MEDICAL MICROBIOLOGY AND IMMUNOLOGY   204 ( 5 )   605 - 612   2015年10月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Porphyromonas gingivalis, a periodontal pathogen, is epidemiologically associated with oral squamous cell carcinoma (OSCC). Matrix metalloproteinase 9 (MMP9) which degrades the extracellular matrix and basement membrane components has been implicated in invasion and metastasis of tumor cells. We previously reported that P. gingivalis promoted cellular invasion of carcinoma SAS cells, an established cell line from patients with squamous cell carcinoma of the tongue, by induction of MMP9 production via proteinase-activated receptor 2. In this study, we further examined alternative signaling pathways mediating inactive precursor of MMP9 (proMMP9) production induced by P. gingivalis in SAS cells. Following P. gingivalis infection, PAR4 mRNA expression was increased and proMMP9 production was enhanced, leading to acceleration of SAS cell invasion. Small interfering RNA knockdown of PAR4 gene abrogated both proMMP9 expression and cellular invasion induced by P. gingivalis in SAS cells. Moreover, the phosphorylation of p38 and ERK1/2 was reduced in PAR4 gene knockdown cells infected with P. gingivalis, whereas nuclear translocation of NF-kB was not inhibited. These results suggest that P. gingivalis activates PAR4 signaling pathways, leading proMMP9 over-expression and cellular invasion in OSCC cells.

    DOI: 10.1007/s00430-015-0389-y

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  • Noncanonical Activation of beta-Catenin by Porphyromonas gingivalis 査読

    Yun Zhou, Maryta Sztukowska, Qian Wang, Hiroaki Inaba, Jan Potempa, David A. Scott, Huizhi Wang, Richard J. Lamont

    INFECTION AND IMMUNITY   83 ( 8 )   3195 - 3203   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Porphyromonas gingivalis is an established pathogen in periodontal disease and an emerging pathogen in serious systemic conditions, including some forms of cancer. We investigated the effect of P. gingivalis on beta-catenin signaling, a major pathway in the control of cell proliferation and tumorigenesis. Infection of gingival epithelial cells with P. gingivalis did not influence the phosphorylation status of beta-catenin but resulted in proteolytic processing. The use of mutants deficient in gingipain production, along with gingipain-specific inhibitors, revealed that gingipain proteolytic activity was required for beta-catenin processing. The beta-catenin destruction complex components Axin1, adenomatous polyposis coli (APC), and GSK3 beta were also proteolytically processed by P. gingivalis gingipains. Cell fractionation and Western blotting demonstrated that beta-catenin fragments were translocated to the nucleus. The accumulation of beta-catenin in the nucleus following P. gingivalis infection was confirmed by immunofluorescence microscopy. A luciferase reporter assay showed that P. gingivalis increased the activity of the beta-catenin-dependent TCF/LEF promoter. P. gingivalis did not increase Wnt3a mRNA levels, a finding consistent with P. gingivalis-induced proteolytic processing causing the increase in TCF/LEF promoter activity. Thus, our data indicate that P. gingivalis can induce the non-canonical activation of beta-catenin and disassociation of the beta-catenin destruction complex by gingipain-dependent proteolytic processing. beta-Catenin activation in epithelial cells by P. gingivalis may contribute to a proliferative phenotype.

    DOI: 10.1128/IAI.00302-15

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  • ヒト胎盤栄養膜細胞におけるP.gingivalis感染がDNA損傷シグナルに及ぼす影響

    稲葉 裕明, 久保庭 雅恵, 天野 敦雄

    Journal of Oral Biosciences Supplement   2012   138 - 138   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Identification of signaling pathways mediating cell cycle arrest and apoptosis induced by Porphyromonas gingivalis in human trophoblasts. 査読

    Inaba H, Kuboniwa M, Sugita H, Lamont RJ, Amano A

    Infection and Immunity   80 ( 8 )   2847 - 2857   2012年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1128/IAI.00258-12

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  • Porphyromonas gingivalis SerB-mediated dephosphorylation of host cell cofilin modulates invasion efficiency 査読

    Catherine E. Moffatt, Hiroaki Inaba, Takanori Hirano, Richard J. Lamont

    CELLULAR MICROBIOLOGY   14 ( 4 )   577 - 588   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Porphyromonas gingivalis, a host-adapted opportunistic pathogen, produces a serine phosphatase, SerB, known to affect virulence, invasion and persistence within the host cell. SerB induces actin filament rearrangement in epithelial cells, but the mechanistic basis of this is not fully understood. Here we investigated the effects of SerB on the actin depolymerizing host protein cofilin. P. gingivalis infection resulted in the dephosphorylation of cofilin in gingival epithelial cells. In contrast, a SerB-deficient mutant of P. gingivalis was unable to cause cofilin dephosphorylation. The involvement of cofilin in P. gingivalis invasion was determined by quantitative image analysis of epithelial cells in which cofilin had been knocked down or knocked in with various cofilin constructs. siRNA-silencing of cofilin led to a significant decrease in numbers of intracellular P. gingivalis marked by an absence of actin colocalization. Transfection with wild-type cofilin or constitutively active cofilin both increased numbers of intracellular bacteria, while constitutively inactive cofilin abrogated invasion. Expression of LIM kinase resulted in reduced P. gingivalis invasion, an effect that was reversed by expression of constitutively active cofilin. These results show that P. gingivalis SerB activity induces dephosphorylation of cofilin, and that active cofilin is required for optimal invasion into gingival epithelial cells.

    DOI: 10.1111/j.1462-5822.2011.01743.x

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  • Proliferation of Smooth Muscle Cells Stimulated by Porphyromonas Gingivalis is Inhibited by Apple Polyphenol 査読

    Hiroaki Inaba, Motoyuki Tagashira, Tomomasa Kanda, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   82 ( 11 )   1616 - 1622   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Porphyromonas gingivalis (Pg) is thought to be involved in the progression of occlusive arterial lesions, whereas vascular smooth muscle cell (SMC) proliferation is considered to be involved in occlusive arterial disease. We previously showed that bacteremia caused by Pg infection induced proliferation of mouse aortic SMCs. Furthermore, human SMCs stimulated with human plasma incubated with Pg showed a marked transformation from the contractile to proliferative phenotype. In the present study, we examine the involvement of Pg gingipains and fimbriae in induction of the SMC transformation and proliferation, and effective inhibitors.
    Methods: Pg strains including gingipain-and fimbria-null mutants were incubated in human plasma, after which the bacteria were removed and the supernatants were added to cultured SMCs. To evaluate the effects of inhibitors, Pg organisms were incubated in plasma in the presence of apple polyphenol (AP), epigallocatechin gallate, KYT-1 (Arg-gingipain inhibitor), and KYT-36 (Lys-gingipain inhibitor).
    Results: Plasma supernatants from wild-type and fimbriamutant cultures markedly stimulated cellular proliferation, whereas those containing gingipain-null mutants showed negligible effects. SMC proliferation was also induced by plasma treated with trypsin. Furthermore, plasma supernatants cultured in the presence of KYT-1/KYT-36 and AP showed significant inhibitory effects on SMC proliferation, whereas cultures with epigallocatechin gallate did not.
    Conclusion: Our results suggest that Pg gingipains are involved in the induction of SMC transformation and proliferation, whereas this was inhibited by AP. J Periodontol 2011;82:1616-1622.

    DOI: 10.1902/jop.2011.100785

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  • Characterization of aortic aneurysms in cardiovascular disease patients harboring Porphyromonas gingivalis 査読

    Nakano K, Wada K, Nomura R, Nemoto H, Inaba H, Kojima A, Naka S, Hokamura K, Mukai T, Nakajima A, Umemura K, Kamisaki Y, Yoshioka H, Taniguchi K, Amano A, Ooshima T

    Oral Diseases   17 ( 4 )   370 - 378   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1601-0825.2010.01759.x

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  • 歯周病と4つの全身疾患

    天野 敦雄, 稲葉 裕明

    臨床薬理 = Japanese journal of clinical pharmacology   42 ( 2 )   65 - 66   2011年3月

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    記述言語:日本語   出版者・発行元:The Japanese Society of Clinical Pharmacology and Therapeutics  

    DOI: 10.3999/jscpt.42.65

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    その他リンク: http://search.jamas.or.jp/link/ui/2011173700

  • Porphyromonas gingivalisの細胞内動態の解析

    竹内 洋輝, 加藤 隆大, 稲葉 裕明, 村上 旬平, 秋山 茂久, 森崎 市治郎, 天野 敦雄

    障害者歯科   30 ( 3 )   512 - 512   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本障害者歯科学会  

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  • 線毛遺伝子型の形質転換により変化するPorphyromonas gingivalisの病原性

    加藤 隆大, 稲葉 裕明, 秋山 茂久, 森崎 市治郎, 天野 敦雄

    障害者歯科   26 ( 3 )   393 - 393   2005年9月

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    記述言語:日本語   出版者・発行元:(一社)日本障害者歯科学会  

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  • フェニトイン刺激された歯肉線維芽細胞のコラーゲン代謝に及ぼすTNF-αの影響

    天野 敦雄, 加藤 隆大, 稲葉 裕明, 秋山 茂久, 森崎 市治郎

    障害者歯科   26 ( 3 )   394 - 394   2005年9月

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    記述言語:日本語   出版者・発行元:(一社)日本障害者歯科学会  

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  • ダウン症候群歯肉線維芽細胞の歯周病原細菌に対する易感染性

    村上旬平, 岡田直子, 堤香奈子, 加藤隆大, 稲葉裕明, 秋山茂久, 天野敦雄, 森崎市治郎

    障害者歯科25巻3号 Page294   25 ( 3 )   294 - 294   2004年10月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)   出版者・発行元:(一社)日本障害者歯科学会  

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  • 2型糖尿病患者における歯周炎とPorphyromonas gingivalis線毛遺伝子多型との関連

    竹田宗弘, 小島美樹, 久保庭雅恵, 稲葉裕明, 雫石聡, 天野敦雄

    日本口腔衛生学会雑誌   2003年9月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • ヒト歯肉線維芽細胞によるMMP発現への抗てんかん薬フェニトインの影響

    加藤隆大, 稲葉裕明, 久保庭雅恵, 天野敦雄

    日本口腔衛生学会雑誌   2003年9月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • 歯根膜細胞へのエムドゲインの作用に対するPorphyromonas gingivalisの影響

    稲葉裕明, 加藤隆大, 天野敦雄

    日本口腔衛生学会雑誌   2003年9月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • P. gingivalis prevents the efficacy of enamel matrix derivative.

    Inaba H, Okahashi N, Nakayama N, Amano A

    Journal of Dental Research   2003年6月

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    記述言語:英語   掲載種別:研究論文(その他学術会議資料等)  

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  • P. gingivalis 感染によるマウス骨芽細胞からの RANKL 発現

    岡橋暢夫, 稲葉裕明, 中川一路, 山村泰平, 天野敦雄, 浜田茂幸

    第76回日本細菌学会総会   2003年4月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • フェニトインのヒト歯肉線維芽細胞MMP発現への影響 招待

    加藤隆大, 稲葉裕明, 高田勇之助, 村上旬平, 天野敦雄, 森崎市治郎

    2002年10月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • 薬物誘発性歯肉肥大患者検出された歯周病原性菌のreal-time PCR法による定量.

    木村啓次リチャード, 秋山茂久, 村上旬平, 上田甲寅, 稲葉裕明, 天野敦雄, 森崎市治郎

    障害者歯科23巻3号 275   23 ( 3 )   275 - 275   2002年9月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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  • 塩基性ペプチド・プロタミンのヒト歯肉線維芽細胞に対する作用

    稲葉裕明, 村上旬平, 加藤隆大, 高田勇之介, 天野敦雄, 森崎市治郎

    障害者歯科   2002年9月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

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▼全件表示

MISC

  • Streptococcus mutans コラーゲン結合タンパク Cnm の構造および機能の検討

    松岡大貴, 仲 周平, 後藤花奈, 稲葉裕明, 仲野道代

    岡山歯学会   41 ( 2 )   62 - 62   2022年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • 多嚢胞性脳軟化症患児口腔内における多数歯埋伏の1例

    仲周平, 吉田翔, 松三友紀, 稲葉裕明, 仲野道代

    日本小児歯科学会中四国地方会大会   2022年11月

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  • Streptococcus mutansのコラーゲン結合タンパクCnmの構造解析

    松岡大貴, 仲周平, 稲葉裕明, 仲野道代

    日本小児歯科学会中四国地方会大会   2022年11月

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  • 非アルコール性脂肪肝炎患者口腔由来Streptococcus mutansの脂肪酸結合能の評価

    田畑佳子, 中野聡大, 仲周平, 稲葉裕明, 仲野道代

    日本小児歯科学会中四国地方会大会   2022年11月

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  • 口腔細菌が頭頸部癌細胞株に及ぼす影響と予後との関連性

    西山今日子, 稲葉裕明, 濱田正和, 吉田 翔, 仲野道代

    歯科基礎医学会   2022年9月

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  • 血清飢餓状態が頭頸部癌細胞株に及ぼす影響と飢餓誘導遺伝子の予後との関連性

    西山今日子, 稲葉裕明, 濱田正和, 吉田 翔, 仲野道代, 鵜澤成一

    歯科基礎医学会   2021年10月

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  • Porphyromonas gulae線毛遺伝子多型のバイオフィルム形成能への影響

    吉田翔, 稲葉裕明, 仲野道代

    歯科基礎医学会   2021年10月

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  • Porphyromonas gulae LPS 誘発炎症反応における緑茶ポリフェノールの抗炎症作用

    稲葉裕明, 吉田翔, 仲野道代

    歯科基礎医学会   2021年10月

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  • 血清飢餓状態が頭頸部癌細胞株に及ぼす影響と飢餓誘導遺伝子の予後との関連性(Effect of serum starvation on head and neck cancer cell lines and prognostic association of starvation-induced genes)

    西山 今日子, 稲葉 裕明, 濱田 正和, 吉田 翔, 仲野 道代

    Journal of Oral Biosciences Supplement   2021   197 - 197   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Porphyromonas gulae線毛遺伝子多型のバイオフィルム形成能への影響(Effects of FimA variations on biofilm formation by Porphyromonas gulae)

    吉田 翔, 稲葉 裕明, 仲野 道代

    Journal of Oral Biosciences Supplement   2021   187 - 187   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 岡山大学病院における抗菌薬適正使用支援チーム(AST)の取り組みと評価

    東恩納司, 森下陽介, 稲葉裕明, 草野展周, 塚原宏一

    日本環境感染学会   2021年9月

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  • 岡山大学病院での急性単純性膀胱炎に対する尿検査実施状況および経口抗菌薬の処方動向に関する実態調査

    森下陽介, 東恩納司, 稲葉裕明, 草野展周, 塚原宏一

    日本環境感染学会   2021年9月

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  • 東恩納司、岡崎昌利、稲葉裕明、飯尾耕治、筧彩佳、宮村純子、草野展周、塚原宏一

    岡山大学病院外来歯科領域における経口第三世代セフェム経口抗菌薬の使用量の削減について

    日本環境感染学会   2020年2月

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  • VREのアウトブレイク事例とその解析

    筧彩佳, 宮村純子, 飯尾耕治, 東恩納司, 岡崎昌利, 稲葉裕明, 草野展周, 塚原宏一

    日本環境感染学会   2020年2月

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  • 岡山大学病院外来歯科領域における経口第三世代セフェム系抗菌薬の使用量の削減について

    東恩納 司, 岡崎 昌利, 稲葉 裕明, 飯尾 耕二, 筧 彩佳, 宮村 純子, 草野 展周, 塚原 宏一, 千堂 年昭

    日本環境感染学会総会プログラム・抄録集   35回   P5 - 7   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • サイクロデキストランがStreptococcus mutansのバイオフィルム形成に与える影響

    浅海春華, 松三友紀, 高島由紀子, 仲周平, 稲葉裕明, 仲野道代

    岡山歯学会雑誌   38 ( 2 )   2019年

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  • 急速な骨吸収により乳歯の早期脱落を来した小児の1例

    田畑佳子, 吉田衣里, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   57 ( 1 )   2019年

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  • 造血幹細胞移植施行患者における口腔レンサ球菌の分布

    森川優子, 吉田衣里, 角田陽子, 高島由紀子, 平野慶子, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   57 ( 1 )   2019年

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  • 生体機能性材料S-PRGフィラーが口腔バイオフィルム形成に与える影響

    高島 由紀子, 森川 優子, 森本 節代, 稲葉 裕明, 仲野 道代

    小児歯科学雑誌   56 ( 2 )   237 - 237   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • 当院外来における経口抗菌薬の使用実態調査と適正使用に向けた今後の課題

    東恩納 司, 岡崎 昌利, 田坂 健, 宮村 純子, 能勢 資子, 稲葉 裕明, 草野 展周, 千堂 年昭

    日本環境感染学会総会プログラム・抄録集   33回   357 - 357   2018年2月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 化学療法中の小児に発症する口腔粘膜疾患の臨床調査

    森川優子, 吉田衣里, 角田陽子, 高島由紀子, 平野慶子, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   56 ( 1 )   2018年

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  • 口腔内のC.rectusとcnm遺伝子陽性S.mutansの存在はIgA腎症患者の蛋白尿を増悪させる

    三崎太郎, 仲周平, 和唐薫子, 畠山理那, 長澤康行, 伊藤誓悟, 稲葉裕明, 野村良太, 仲野道代, 仲野和彦

    IgA腎症研究会学術集会抄録   41st   2018年

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  • 扁桃におけるコラーゲン結合タンパク陽性Streptococcus mutansの存在はIgA腎症の発症および蛋白尿と関連する

    伊藤誓悟, 三崎太郎, 野村良太, 大継將寿, 山形瑛, 松原秀史, 今給黎敏彦, 大島直紀, 仲周平, 和唐薫子, 畠山理那, 長澤康行, 稲葉裕明, 仲野道代, 仲野和彦, 熊谷裕生

    日本腎臓学会誌   60 ( 3 )   2018年

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  • 生体機能性材料S-PRGフィラーが口腔バイオフィルムに与える影響

    森川優子, 高島由紀子, 仲周平, 稲葉裕明, 仲野道代

    岡山歯学会雑誌   37 ( 2 )   2018年

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  • 乳酸菌由来のバクテリオシンがStreptococcus mutansのバイオフィルム形成に与える影響

    森本節代, 森川優子, 高島由紀子, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   56 ( 2 )   2018年

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  • 歯肉増殖を認める多嚢胞性脳軟化症患児の1例

    仲周平, 吉田翔, 角田陽子, 稲葉裕明, 仲野道代

    小児歯科学雑誌   56 ( 1 )   2018年

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  • 造血幹細胞移植を施行された患児の歯科的管理について

    吉田衣里, 森川優子, 松三友紀, 高島由紀子, 平野慶子, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   56 ( 1 )   2018年

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  • 歯周病原性菌C.rectusと齲蝕原性菌cnm遺伝子陽性S.mutansの口腔内の存在はIgA腎症患者の蛋白尿と関連する

    三崎太郎, 塩岡天平, 千葉圭, 小野雅史, 鈴木由美子, 磯崎泰介, 仲周平, 和唐薫子, 畠山理那, 長澤康行, 伊藤誓悟, 稲葉裕明, 野村良太, 仲野道代, 仲野和彦

    日本腎臓学会誌   60 ( 3 )   2018年

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  • 乳酸菌が産生するバクテリオシンが口腔バイオフィルム形成に与える影響

    森本節代, 森川優子, 高島由紀子, 仲周平, 稲葉裕明, 仲野道代

    小児歯科学雑誌   56 ( 1 )   2018年

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  • 本院小児医療センター開設後の当科における患者実態調査

    高島 由紀子, 吉田 翔, 森本 節代, 吉田 衣里, 角田 陽子, 平野 慶子, 稲葉 裕明, 仲野 道代

    小児歯科学雑誌   55 ( 1 )   137 - 137   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation

    Hiroaki Inaba, Hideyuki Sugita, Masae Kuboniwa, Soichi Iwai, Masakazu Hamada, Takeshi Noda, Ichijiro Morisaki, Richard J. Lamont, Atsuo Amano

    CELLULAR MICROBIOLOGY   16 ( 1 )   131 - 145   2014年1月

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    記述言語:英語   出版者・発行元:WILEY  

    Recent epidemiological studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, matrix metalloproteinase 9 (MMP9) is implicated in the invasion and metastasis of tumour cells. We examined the involvement of Porphyromonas gingivalis, a periodontal pathogen, in OSCC invasion through induced expression of proMMP and its activation. proMMP9 was continuously secreted from carcinoma SAS cells, while P.gingivalis infection increased proenzyme expression and subsequently processed it to active MMP9 in culture supernatant, which enhanced cellular invasion. In contrast, Fusobacterium nucleatum, another periodontal organism, failed to demonstrate such activities. The effects of P.gingivalis were observed with highly invasive cells, but not with the low invasivetype. P.gingivalis also stimulated proteinase-activated receptor 2 (PAR2) and enhanced proMMP9 expression, which promoted cellular invasion. P.gingivalis mutants deficient in gingipain proteases failed to activate MMP9. Infected SAS cells exhibited activation of ERK1/2, p38, and NF-kB, and their inhibitors diminished both proMMP9-overexpression and cellular invasion. Together, our results show that P.gingivalis activates the ERK1/2-Ets1, p38/HSP27, and PAR2/NF-kB pathways to induce proMMP9 expression, after which the proenzyme is activated by gingipains to promote cellular invasion of OSCC cell lines. These findings suggest a novel mechanism of progression and metastasis of OSCC associated with periodontitis.

    DOI: 10.1111/cmi.12211

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  • O-26 歯肉上皮細胞由来ポリアミンがPorphyromonas gingivalisの病原性に及ぼす影響(一般口演)

    久保庭 雅恵, Samar Alghamdi, 稲葉 裕明, 橋野 恵衣, 天野 敦雄

    口腔衛生学会雑誌   63 ( 2 )   158 - 158   2013年4月

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    記述言語:日本語   出版者・発行元:有限責任中間法人日本口腔衛生学会  

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  • P-84 Porphyromonas gingivalis感染がヒト口腔癌細胞の浸潤能に及ぼす影響(ポスター)

    稲葉 裕明, 久保庭 雅恵, 天野 敦雄

    口腔衛生学会雑誌   63 ( 2 )   209 - 209   2013年4月

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    記述言語:日本語   出版者・発行元:有限責任中間法人日本口腔衛生学会  

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  • Distribution and molecular characterization of Porphyromonas gulae carrying a new fimA genotype

    Yoshie Yamasaki, Yoshie Yamasaki, Ryota Nomura, Kazuhiko Nakano, Hiroaki Inaba, Masae Kuboniwa, Norihiko Hirai, Mitsuyuki Shirai, Yukio Kato, Masaru Murakami, Shuhei Naka, Soichi Iwai, Michiyo Matsumoto-Nakano, Takashi Ooshima, Atsuo Amano, Fumitoshi Asai

    Veterinary Microbiology   161 ( 1-2 )   196 - 205   2012年12月

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    記述言語:英語  

    Porphyromonas gulae is a gram-negative black-pigmented anaerobe which is known to be a pathogen for periodontitis in dogs. Approximately 41. kDa filamentous appendages on the cell surface (FimA) encoded by the fimA gene are regarded as important factors associated with periodontitis. The fimA genotype was classified into two major types and strains in type B were shown to be more virulent than those in type A. In the present study, we characterized a strain with a novel fimA genotype and designated it as type C. The putative amino acid sequence was shown to be similar to the genotype IV fimA of Porphyromonas gingivalis, a major pathogen of human periodontitis. Analyses using an oral squamous cell carcinoma cell line derived from tongue primary lesions revealed that the type C strain inhibited proliferation and scratch closure more than genotype A and B strains. In addition, experiments using a mouse abscess model demonstrated that the type C strain could induce much higher systemic inflammation when compared with strains of the other genotypes. Furthermore, molecular analyses of oral swab specimens collected from dogs demonstrated that the detection frequencies of P. gulae and the genotype C in the periodontitis group were significantly higher than those in the periodontally healthy group. These results suggest that FimA of P. gulae is diverse with the virulence of genotype C strains the highest and that molecular identification of genotype C P. gulae could be a possible useful marker for identifying dogs at high risk of developing periodontitis. © 2012 Elsevier B.V.

    DOI: 10.1016/j.vetmic.2012.07.026

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  • ヒト胎盤栄養膜細胞におけるP.gingivalis感染がDNA損傷シグナルに及ぼす影響

    稲葉裕明, 久保庭雅恵, 天野敦雄

    Journal of Oral Biosciences Supplement (Web)   2012   2012年

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  • 歯肉上皮細胞p53タンパクへの Porphyromonas gingivalis 感染の影響

    杉田 英之, 稲葉 裕明, 天野 敦雄, 森崎 市治郎

    障害者歯科   32 ( 3 )   458 - 458   2011年9月

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  • Molecular analysis of aortic intimal hyperplasia caused by Porphyromonas gingivalis infection in mice with endothelial damage

    K. Hokamura, H. Inaba, K. Nakano, R. Nomura, H. Yoshioka, K. Taniguchi, T. Ooshima, K. Wada, A. Amano, K. Umemura

    JOURNAL OF PERIODONTAL RESEARCH   45 ( 3 )   337 - 344   2010年6月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Objective:
    Porphyromonas gingivalis infection is thought to be a significant etiological factor in the development of cardiovascular diseases. However, scant definitive evidence has been presented concerning the pathological molecular mechanisms of these disorders. In the present study, we performed a molecular analysis of the developmental mechanisms of aortic intimal hyperplasia induced by P. gingivalis.
    Material and Methods:
    The effects of P. gingivalis-induced bacteremia on intimal hyperplasia were evaluated using a mouse model of aortic hyperplasia created by photochemical-induced endothelial cell injury. Alterations of gene expression profiles in injured blood vessels of the mice were extensively analyzed using DNA microarray assays to identify the key molecules involved in P. gingivalis-induced hyperplasia. In addition, human aneurismal specimens from patients with or without P. gingivalis infection were analyzed histochemically.
    Results:
    Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model. Concomitantly, S100 calcium-binding protein A9 (S100A9) and embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients.
    Conclusion:
    We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.

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  • Molecular analysis of aortic intimal hyperplasia caused by Porphyromonas gingivalis infection in mice with endothelial damage

    K. Hokamura, H. Inaba, K. Nakano, R. Nomura, H. Yoshioka, K. Taniguchi, T. Ooshima, K. Wada, A. Amano, K. Umemura

    JOURNAL OF PERIODONTAL RESEARCH   45 ( 3 )   337 - 344   2010年6月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Objective:
    Porphyromonas gingivalis infection is thought to be a significant etiological factor in the development of cardiovascular diseases. However, scant definitive evidence has been presented concerning the pathological molecular mechanisms of these disorders. In the present study, we performed a molecular analysis of the developmental mechanisms of aortic intimal hyperplasia induced by P. gingivalis.
    Material and Methods:
    The effects of P. gingivalis-induced bacteremia on intimal hyperplasia were evaluated using a mouse model of aortic hyperplasia created by photochemical-induced endothelial cell injury. Alterations of gene expression profiles in injured blood vessels of the mice were extensively analyzed using DNA microarray assays to identify the key molecules involved in P. gingivalis-induced hyperplasia. In addition, human aneurismal specimens from patients with or without P. gingivalis infection were analyzed histochemically.
    Results:
    Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model. Concomitantly, S100 calcium-binding protein A9 (S100A9) and embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients.
    Conclusion:
    We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.

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  • Roles of Oral Bacteria in Cardiovascular Diseases - From Molecular Mechanisms to Clinical Cases: Implication of Periodontal Diseases in Development of Systemic Diseases

    Hiroaki Inaba, Atsuo Amano

    JOURNAL OF PHARMACOLOGICAL SCIENCES   113 ( 2 )   103 - 109   2010年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

    Periodontal diseases, some of the most common infectious diseases seen in humans, are characterized by gingival inflammation, as well as loss of connective tissue and bone from around the roots of the teeth, which leads to eventual tooth exfoliation. In the past decade, the association of periodontal diseases with the development of systemic diseases has received increasing attention. Although a number of studies have presented evidence of close relationships between periodontal and systemic diseases, the majority of Findings are limited to epidemiological studies, while the etiological details remain unclear. Nevertheless, a variety of recent hypothesis driven investigations have compiled various results showing that periodontal infection and subsequent direct oral-hematogenous spread of bacteria are implicated in the development of various systemic diseases. Herein, we present current understanding in regard to the relationship between periodontal and systemic diseases, including cardiovascular diseases, preterm delivery of low birth weight, diabetes mellitus, respiratory diseases, and osteoporosis.

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  • Genotyping to distinguish microbial pathogenicity in periodontitis

    Periodontology 2000   54: 136-159   2010年

  • Genotyping to distinguish microbial pathogenicity in periodontitis

    Periodontology 2000   54: 136-159   136 - 159   2010年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

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  • Roles of oral bacteria in cardiovascular diseases - From molecular mechanisms to clinical cases: Implication of periodontal diseases in development of systemic diseases

    Journal of Pharmacological Sciences   113(2), 103-109   2010年

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  • Porphyromonas gingivalis invades human trophoblasts and inhibits proliferation by inducing G1 arrest and apoptosis

    Hiroaki Inaba, Masae Kuboniwa, Brian Bainbridge, Oezlem Yilmaz, Joseph Katz, Kathleen T. Shiverick, Atsuo Amano, Richard J. Lamont

    CELLULAR MICROBIOLOGY   11 ( 10 )   1517 - 1532   2009年10月

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    記述言語:英語   出版者・発行元:WILEY  

    P&gt;Porphyromonas gingivalis is an oral pathogen that is also associated with serious systemic conditions such as preterm delivery. Here we investigated the interaction between P. gingivalis and a cell line of extravillous trophoblasts (HTR-8) derived from the human placenta. P. gingivalis internalized within HTR-8 cells and inhibited proliferation through induction of arrest in the G1 phase of the cell cycle. G1 arrest was associated with decreased expression of cyclin D and of CDKs 2, 4 and 6. In addition, levels of CDK inhibitors p15, p16, p18 and p21 were increased following P. gingivalis infection. The amount of Rb was diminished by P. gingivalis, and transient overexpression of Rb, with concomitant upregulation of phospho-Rb, relieved P. gingivalis-induced G1 arrest. HTR-8 cells halted in the G1 phase became apoptotic, and apoptosis was accompanied by an increase in the ratio of Bax/Bcl-2 and increased activity of caspases 3, 7 and 9. HTR-8 cells infected with P. gingivalis also exhibited a sustained activation of ERK1/2, and knock-down of ERK1/2 activity with siRNA abrogated both G1 arrest and apoptosis. Thus, P. gingivalis can invade placental trophoblasts and induce G1 arrest and apoptosis through pathways involving ERK1/2 and its downstream effectors, properties that provide a mechanistic basis for pathogenicity in complications of pregnancy.

    DOI: 10.1111/j.1462-5822.2009.01344.x

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  • Porphyromonas gingivalis invades human trophoblasts and inhibits proliferation by inducing G1 arrest and apoptosis

    Hiroaki Inaba, Masae Kuboniwa, Brian Bainbridge, Oezlem Yilmaz, Joseph Katz, Kathleen T. Shiverick, Atsuo Amano, Richard J. Lamont

    CELLULAR MICROBIOLOGY   11 ( 10 )   1517 - 1532   2009年10月

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    記述言語:英語   出版者・発行元:WILEY  

    P&gt;Porphyromonas gingivalis is an oral pathogen that is also associated with serious systemic conditions such as preterm delivery. Here we investigated the interaction between P. gingivalis and a cell line of extravillous trophoblasts (HTR-8) derived from the human placenta. P. gingivalis internalized within HTR-8 cells and inhibited proliferation through induction of arrest in the G1 phase of the cell cycle. G1 arrest was associated with decreased expression of cyclin D and of CDKs 2, 4 and 6. In addition, levels of CDK inhibitors p15, p16, p18 and p21 were increased following P. gingivalis infection. The amount of Rb was diminished by P. gingivalis, and transient overexpression of Rb, with concomitant upregulation of phospho-Rb, relieved P. gingivalis-induced G1 arrest. HTR-8 cells halted in the G1 phase became apoptotic, and apoptosis was accompanied by an increase in the ratio of Bax/Bcl-2 and increased activity of caspases 3, 7 and 9. HTR-8 cells infected with P. gingivalis also exhibited a sustained activation of ERK1/2, and knock-down of ERK1/2 activity with siRNA abrogated both G1 arrest and apoptosis. Thus, P. gingivalis can invade placental trophoblasts and induce G1 arrest and apoptosis through pathways involving ERK1/2 and its downstream effectors, properties that provide a mechanistic basis for pathogenicity in complications of pregnancy.

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  • Homotypic biofilm structure of Porphyromonas gingivalis is affected by FimA type variations

    M. Kuboniwa, A. Amano, H. Inaba, E. Hashino, S. Shizukuishi

    Oral Microbiology and Immunology   24 ( 3 )   260 - 263   2009年6月

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    記述言語:英語  

    Introduction: Porphyromonas gingivalis is a periodontal pathogen whose long fimbriae (FimA) are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes. FimA variations were previously shown to be related to the onset and development of adult periodontitis in a general population, while FimA were recently found to be critical mediators of initial biofilm formation. However, it is unclear if FimA variations have effects on biofilm features. Here, we compare the characteristic structures of homotypic biofilms developed by P. gingivalis strains with different FimA types. Methods: Biofilms were formed on saliva-coated glass bottom wells in phosphate-buffered saline and their structures were analysed using confocal laser scanning microscopy. Furthermore, the biovolumes of the biofilms were quantified with a three-dimensional fluorophotometric method. Results: Biofilm structures formed by the six representative FimA-type strains apparently differed. Type I and Ib P. gingivalis formed biofilms with a dense basal monolayer and dispersed microcolonies, whereas those formed by types II, III and IV strains had markedly luxuriant biofilms filled with widely clumped and tall colonies, and their biovolumes were significantly greater than those of types I and Ib. These characteristic features were confirmed to be closely related to FimA type in assays that utilized fimA-substituted mutants from type I to II and those from type II to I. Conclusion: Our results suggest that FimA variations have effects on the structures of biofilms formed by P. gingivalis, which may be an important factor in the pathogenesis of periodontitis. © 2009 John Wiley and Sons A/S.

    DOI: 10.1111/j.1399-302X.2009.00511.x

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  • Distinct roles of long/short fimbriae and gingipains in homotypic biofilm development by Porphyromonas gingivalis

    Masae Kuboniwa, Atsuo Amano, Ei Hashino, Yumiko Yamamoto, Hiroaki Inaba, Nobushiro Hamada, Koji Nakayama, Gena D. Tribble, Richard J. Lamont, Satoshi Shizukuishi

    BMC MICROBIOLOGY   9 ( 9 )   105   2009年5月

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    記述言語:英語   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Porphyromonas gingivalis, a periodontal pathogen, expresses a number of virulence factors, including long ( FimA) and short (Mfa) fimbriae as well as gingipains comprised of arginine-specific (Rgp) and lysine-specific (Kgp) cysteine proteinases. The aim of this study was to examine the roles of these components in homotypic biofilm development by P. gingivalis, as well as in accumulation of exopolysaccharide in biofilms.
    Results: Biofilms were formed on saliva-coated glass surfaces in PBS or diluted trypticase soy broth (dTSB). Microscopic observation showed that the wild type strain formed biofilms with a dense basal monolayer and dispersed microcolonies in both PBS and dTSB. A FimA deficient mutant formed patchy and small microcolonies in PBS, but the organisms proliferated and formed a cohesive biofilm with dense exopolysaccharides in dTSB. A Mfa mutant developed tall and large microcolonies in PBS as well as dTSB. A Kgp mutant formed markedly thick biofilms filled with large clumped colonies under both conditions. A RgpA/B double mutant developed channel-like biofilms with fibrillar and tall microcolonies in PBS. When this mutant was studied in dTSB, there was an increase in the number of peaks and the morphology changed to taller and loosely packed biofilms. In addition, deletion of FimA reduced the autoaggregation efficiency, whereas autoaggregation was significantly increased in the Kgp and Mfa mutants, with a clear association with alteration of biofilm structures under the non-proliferation condition. In contrast, this association was not observed in the Rgp-null mutants.
    Conclusion: These results suggested that the FimA fimbriae promote initial biofilm formation but exert a restraining regulation on biofilm maturation, whereas Mfa and Kgp have suppressive and regulatory roles during biofilm development. Rgp controlled microcolony morphology and biovolume. Collectively, these molecules seem to act coordinately to regulate the development of mature P. gingivalis biofilms.

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  • Detection of oral bacteria in cardiovascular specimens

    K. Nakano, H. Nemoto, R. Nomura, H. Inaba, H. Yoshioka, K. Taniguchi, A. Amano, T. Ooshima

    ORAL MICROBIOLOGY AND IMMUNOLOGY   24 ( 1 )   64 - 68   2009年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Oral bacteria, including cariogenic and periodontal pathogens, are thought to be etiological factors in the development of cardiovascular diseases. To define this relationship, we analyzed the distribution of oral bacterial species in cardiovascular specimens.
    Following acceptance into the study, 203 consecutive patients were analyzed, from whom 82 aortic valve specimens, 35 mitral valve specimens, and 86 aortic aneurysmal wall specimens, of which 16 contained aneurysmal thrombus tissues, were obtained. In addition, a total of 58 dental plaque specimens were collected from the same group of patients who underwent heart valve replacement or removal of aortic aneurysms. Bacterial DNA was extracted from both cardiovascular tissues and dental plaque in those cases and then species-specific polymerase chain reaction assays were used to analyze the occurrences of six oral streptococcal and six periodontal bacterial species.
    Streptococcus mutans was the most frequently detected species in the cardiovascular specimens, followed by Aggregatibacter actinomycetemcomitans. As for dental plaque specimens from patients who underwent cardiovascular operations, most of the tested periodontitis-related species as well as oral streptococci were detected at high frequencies. Furthermore, the positive rate of S. mutans in cardiovascular specimens from patients whose dental plaque specimens were also positive for S. mutans was 78%, which was significantly higher than any other tested species when the same analysis was performed.
    Our results suggest that specific oral bacterial species, such as S. mutans and A. actinomycetemcomitans, are related to bacteremia and may be etiologic factors for the development of cardiovascular diseases.

    DOI: 10.1111/j.1399-302X.2008.00479.x

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  • Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen

    Hiroaki Inaba, Kazuya Hokamura, Kazuhiko Nakano, Ryota Nomura, Kazufumi Katayama, Atsushi Nakajima, Hideo Yoshioka, Kazuhiro Taniguchi, Yoshinori Kamisaki, Takashi Ooshima, Kazuo Umemura, Ferid Murad, Koichiro Wada, Atsuo Amano

    FEBS LETTERS   583 ( 1 )   128 - 134   2009年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    We investigated the effect of a periodontal pathogen, Porphyromonas gingivalis, on human aortic smooth muscle cell (hAOSMC) proliferation as mechanisms of atherosclerosis. Cultured hAOSMCs exposed to the supernatant of plasma incubated with P. gingivalis showed a marked transformation from a contractile to proliferative phenotype, resulting in enhancement of cell growth. DNA micro-array analysis revealed a P. gingivalis-dependent upregulation of S100A9 in hAOSMCs. Small interference-RNA for S100A9 dramatically attenuated the effect of P. gingivalis on transformation and proliferation of hAOSMCs. Our data suggested that upregulation of S100A9 mediated by P. gingivalis is an important event in the development of aortic intimal hyperplasia. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    DOI: 10.1016/j.febslet.2008.11.036

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  • Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen

    Hiroaki Inaba, Kazuya Hokamura, Kazuhiko Nakano, Ryota Nomura, Kazufumi Katayama, Atsushi Nakajima, Hideo Yoshioka, Kazuhiro Taniguchi, Yoshinori Kamisaki, Takashi Ooshima, Kazuo Umemura, Ferid Murad, Koichiro Wada, Atsuo Amano

    FEBS LETTERS   583 ( 1 )   128 - 134   2009年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    We investigated the effect of a periodontal pathogen, Porphyromonas gingivalis, on human aortic smooth muscle cell (hAOSMC) proliferation as mechanisms of atherosclerosis. Cultured hAOSMCs exposed to the supernatant of plasma incubated with P. gingivalis showed a marked transformation from a contractile to proliferative phenotype, resulting in enhancement of cell growth. DNA micro-array analysis revealed a P. gingivalis-dependent upregulation of S100A9 in hAOSMCs. Small interference-RNA for S100A9 dramatically attenuated the effect of P. gingivalis on transformation and proliferation of hAOSMCs. Our data suggested that upregulation of S100A9 mediated by P. gingivalis is an important event in the development of aortic intimal hyperplasia. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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  • Periodontal pathogens: From oral biofilm to systemic diseases

    Atsuo Amano, Hiroaki Inaba

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   26P - 26P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Porphyromonas gingivalis gingipains cause G(1) arrest in osteoblastic/stromal cells (vol 23, pg 158, 2008)

    T. Kato, T. Tsuda, H. Inaba, S. Kawai, N. Okahashi, Y. Shibata, Y. Abiko, A. Amano

    ORAL MICROBIOLOGY AND IMMUNOLOGY   23 ( 5 )   440 - 440   2008年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Distribution of Porphyromonas gingivalis fimA genotypes in cardiovascular specimens from Japanese patients

    K. Nakano, H. Inaba, R. Nomura, H. Nemoto, H. Takeuchi, H. Yoshioka, K. Toda, K. Taniguchi, A. Amano, T. Ooshima

    ORAL MICROBIOLOGY AND IMMUNOLOGY   23 ( 2 )   170 - 172   2008年4月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Introduction: Porphyromonas gingivalis, a major periodontal pathogen, is gaining increasing attention for its possible association with cardiovascular diseases. Its fimbriae are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. In this study, fimA genotypic distribution was analyzed in P. gingivalis-infected cardiovascular specimens.
    Methods: A total of 112 heart valves and 80 atheromatous plaque specimens were collected from patients undergoing cardiovascular surgery, as well as 56 dental plaque specimens. Bacterial DNA was extracted from each, and polymerase chain reaction analysis was carried out with a P. gingivalis-specific set of primers. P. gingivalis-positive specimens were further analyzed to discriminate the fimA genotype using polymerase chain reaction with fimA type-specific primer sets.
    Results: P. gingivalis was detected in 10.4% of the cardiovascular specimens and 50.0% of the dental plaque samples. In the latter, type II was most frequently detected (35.7%), followed by types I (28.6%) and IV (21.4%), while types IV and II were detected with considerable frequencies of 45.0% and 30.0%, respectively, in the cardiovascular specimens. In contrast, the occurrence of type I was limited (5.0%) in the cardiovascular specimens.
    Conclusion: These results suggest that specific fimA genotypic clones, which are reportedly associated with periodontitis, are also frequently harbored in cardiovascular specimens, indicating the possible involvement of type II and IV clones in the initiation and progression of cardiovascular diseases.

    DOI: 10.1111/j.1399-302X.2007.00406.x

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  • Porphyromonas gingivalis gingipains cause G1 arrest in osteoblastic/stromal cells

    T. Kato, T. Tsuda, H. Inaba, S. Kawai, N. Okahashi, Y. Shibata, Y. Abiko, A. Amano

    Oral Microbiology and Immunology   23 ( 2 )   158 - 164   2008年4月

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    記述言語:英語  

    Introduction: The program for mammalian cell growth and division consists of four successive phases
    G1, S, G2, and M. Porphyromonas gingivalis may manipulate the host cell cycle to benefit bacterial virulence expression, which likely causes the cell and tissue tropism observed in chronic periodontal infections. We examined P. gingivalis for its effects on cell-cycle modulation in mouse ST2 osteoblastic/stromal cells. Methods: Synchronized ST2 cells were infected with P. gingivalis ATCC33277 (wild-type, WT), gingipain-mutants [KDP136 (ΔrgpAΔrgpBΔkgp), KDP129 (ΔrgpAΔrgpB), and KDP133 (Δkgp)], and a fimbria-deficient mutant (KDP150) for 24 h, then the cell cycle was evaluated using flow cytometry. Cell-cycle-related molecule expression was examined with a microarray, as well as with quantitative real-time polymerase chain reaction and Western blotting assays. Results: Both the WT and KDP150 strains significantly inhibited cellular proliferation and arrested the cell cycle in the G 0/G1 phase, while the expression levels of the cell-cycle regulatory molecules cyclin D and cyclin E were also decreased. In contrast, KDP136 did not show any effects. G1 arrest was also clearly induced by KDP129 and KDP133, with KDP129 being more effective. Conclusion: The present findings suggest that P. gingivalis gingipains reduce cyclin expression and cause early G1 arrest, leading to the inhibition of cellular proliferation. © 2008 The Authors.

    DOI: 10.1111/j.1399-302X.2007.00405.x

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  • Identification of hop polyphenolic components which inhibit prostaglandin E-2 production by gingival epithelial cells stimulated with periodontal pathogen

    Hiroaki Inaba, Motoyuki Tagashira, Daiki Honma, Tomomasa Kanda, Yurong Kou, Yasuyuki Ohtake, Atsuo Amano

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   31 ( 3 )   527 - 530   2008年3月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Chronic marginal periodontitis is a destructive inflammatory disease caused by an imbalance between bacterial virulence and host defense ability, resulting in eventual tooth exfoliation. Porphyromonas gingivalis, a major periodontal pathogen, triggers a series of cellular inflammatory responses including the production of prostaglandin E-2 (PGE(2)), which causes periodontal destruction; thus, anti-inflammatory reagents are considered beneficial for periodontal therapy. In the present study, we examined whether hop- and apple-derived polyphenols (HBP and ACT, respectively) inhibit PGE(2) production by human gingival epithelial (HGE) cells stimulated with P. gingivalis components. HGE cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP, ACT and epigallocatechin gallate (EGCg) on PGE(2) production by HGE cells were evaluated using an enzyme-linked immunosorbent assay. HBP and EGCg significantly inhibited PGE(2) production, whereas ACT did not. By further fractionation steps of HBP to identify the effective components, 3 components of HBP, 2-[(2-methylpropanoyl)-phloroglucinol]1-O-beta-D-glucopyranoside (MPPG), quercetin 3-O-beta-D-glucopyranoside (iso-quercitrin), and kaempferol 3-O-beta-glucopyranoside (astragalin), were found to be elements which significantly inhibited cellular PGE(2) production. These results suggest that HBP is a potent inhibitor of cellular PGE(2) production induced by P. gingivalis, and HBP may be useful for the prevention and attenuation of periodontitis.

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  • Identification of hop polyphenolic components which inhibit prostaglandin E-2 production by gingival epithelial cells stimulated with periodontal pathogen

    Hiroaki Inaba, Motoyuki Tagashira, Daiki Honma, Tomomasa Kanda, Yurong Kou, Yasuyuki Ohtake, Atsuo Amano

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   31 ( 3 )   527 - 530   2008年3月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Chronic marginal periodontitis is a destructive inflammatory disease caused by an imbalance between bacterial virulence and host defense ability, resulting in eventual tooth exfoliation. Porphyromonas gingivalis, a major periodontal pathogen, triggers a series of cellular inflammatory responses including the production of prostaglandin E-2 (PGE(2)), which causes periodontal destruction; thus, anti-inflammatory reagents are considered beneficial for periodontal therapy. In the present study, we examined whether hop- and apple-derived polyphenols (HBP and ACT, respectively) inhibit PGE(2) production by human gingival epithelial (HGE) cells stimulated with P. gingivalis components. HGE cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP, ACT and epigallocatechin gallate (EGCg) on PGE(2) production by HGE cells were evaluated using an enzyme-linked immunosorbent assay. HBP and EGCg significantly inhibited PGE(2) production, whereas ACT did not. By further fractionation steps of HBP to identify the effective components, 3 components of HBP, 2-[(2-methylpropanoyl)-phloroglucinol]1-O-beta-D-glucopyranoside (MPPG), quercetin 3-O-beta-D-glucopyranoside (iso-quercitrin), and kaempferol 3-O-beta-glucopyranoside (astragalin), were found to be elements which significantly inhibited cellular PGE(2) production. These results suggest that HBP is a potent inhibitor of cellular PGE(2) production induced by P. gingivalis, and HBP may be useful for the prevention and attenuation of periodontitis.

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  • Heterogenic virulence and related factors among clinical isolates of Porphyromonas gingivalis with type II fimbriae

    H. Inaba, K. Nakano, T. Kato, R. Nomura, S. Kawai, M. Kuboniwa, K. Ishihara, T. Ooshima, A. Amano

    ORAL MICROBIOLOGY AND IMMUNOLOGY   23 ( 1 )   29 - 35   2008年2月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Background/aims: Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. Accumulated evidence suggests that P. gingivalis strains with type II fimbriae are more virulent as compared to those with other types. However, it is unknown if strong virulence is uniformly conserved among clones with type II fimbriae. In the present study, we compared infectious inflammatory changes in clinical isolates of P. gingivalis with type II fimbriae using a mouse abscess model to examine their pathogenic heterogeneity and heterogeneity-related factors.
    Methods: Suspensions of nine different clinical isolates with type II fimbriae were subcutaneously injected into female BALB/c mice and inflammatory parameters, such as serum sialic acid concentration, were compared.
    Results: Many of the type II fimbrial isolates caused severe inflammation in the mice, though some were less causative, as was the control strain ATCC 33277 (type I fimbria strain). These results showed that pathogenic heterogeneity exists among P. gingivalis clones with type II fimbriae. Further, the heterogeneity-related factors of P. gingivalis strains were analyzed and the pathogenic potentials showed positive relationships to gingipain activities and invasive efficiency but not to hydrophobicity or autoaggregation. In addition, invasive efficiency was related to the activities of gingipains that were extracellularly secreted.
    Conclusion: These results suggest that pathogenic heterogeneity has relationships with the invasive and proteolytic activities of P. gingivalis clones with type II fimbriae.

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  • Heterogenic virulence and related factors among clinical isolates of Porphyromonas gingivalis with type II fimbriae

    H. Inaba, K. Nakano, T. Kato, R. Nomura, S. Kawai, M. Kuboniwa, K. Ishihara, T. Ooshima, A. Amano

    Oral Microbiology and Immunology   23 ( 1 )   29 - 35   2008年2月

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    記述言語:英語  

    Background/aims: Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. Accumulated evidence suggests that P. gingivalis strains with type II fimbriae are more virulent as compared to those with other types. However, it is unknown if strong virulence is uniformly conserved among clones with type II fimbriae. In the present study, we compared infectious inflammatory changes in clinical isolates of P. gingivalis with type II fimbriae using a mouse abscess model to examine their pathogenic heterogeneity and heterogeneity-related factors. Methods: Suspensions of nine different clinical isolates with type II fimbriae were subcutaneously injected into female BALB/c mice and inflammatory parameters, such as serum sialic acid concentration, were compared. Results: Many of the type II fimbrial isolates caused severe inflammation in the mice, though some were less causative, as was the control strain ATCC 33277 (type I fimbria strain). These results showed that pathogenic heterogeneity exists among P. gingivalis clones with type II fimbriae. Further, the heterogeneity-related factors of P. gingivalis strains were analyzed and the pathogenic potentials showed positive relationships to gingipain activities and invasive efficiency but not to hydrophobicity or autoaggregation. In addition, invasive efficiency was related to the activities of gingipains that were extracellularly secreted. Conclusion: These results suggest that pathogenic heterogeneity has relationships with the invasive and proteolytic activities of P. gingivalis clones with type II fimbriae. © 2008 The Authors.

    DOI: 10.1111/j.1399-302X.2007.00386.x

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  • Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols

    Yurong Kou, Hiroaki Inaba, Takahiro Kato, Motoyuki Tagashira, Daiki Honma, Tornornasa Kanda, Yasuyuki Ohtake, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   79 ( 1 )   174 - 180   2008年1月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Periodontitis is induced by an imbalance between bacterial virulence and host defense ability. Porphyromonas gingivalis, a predominant periodontal pathogen, triggers a series of host inflammatory responses that aggravate the destruction of periodontium. Thus, anti-inflammatory reagents are considered desirable for effective periodontal therapy. In the present study, we examined the inhibitory effects of hop bract polyphenol (HBP) on cellular inflammatory responses induced by P. gingivalis membrane vesicles.
    Methods: Immortalized human gingival epithelial cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP on mRNA expression of cyclooxygenase (COX)-2, interleukin (IL)-6 and -8, and matrix metalloproteinase (MMP)-1 and -3 were examined using real-time reverse transcription-polymerase chain reaction.
    Results: HBP inhibited the mRNA expression of COX-2, IL-6 and -8, and MMP-1 and -3 in a dose-dependent manner, whereas epigallocatechin gallate (a control polyphenol) inhibited COX-2 mRNA expression only. Following further fractionation of HBP to identify the effective components, 2-[(2-methylpropanoyl)-phloroglucinoll 1-O-beta-D-glucopyranoside (MPPG) was identified as a significant anti-inflammatory element that completely inhibited the inflammatory mRNA induction. Kaempferol 3-O-beta-glucopyranoside (astragalin) also was found to have antiinflammatory effects.
    Conclusions: HBP is suggested to be a potent inhibitor of cellular inflammatory responses induced by P. gingivalis vesicles. Further, MPPG and astragalin, identified here as effective components of HBP, also may be useful for the prevention and/or attenuation of periodontitis.

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  • Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols

    Yurong Kou, Hiroaki Inaba, Takahiro Kato, Motoyuki Tagashira, Daiki Honma, Tornornasa Kanda, Yasuyuki Ohtake, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   79 ( 1 )   174 - 180   2008年1月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Periodontitis is induced by an imbalance between bacterial virulence and host defense ability. Porphyromonas gingivalis, a predominant periodontal pathogen, triggers a series of host inflammatory responses that aggravate the destruction of periodontium. Thus, anti-inflammatory reagents are considered desirable for effective periodontal therapy. In the present study, we examined the inhibitory effects of hop bract polyphenol (HBP) on cellular inflammatory responses induced by P. gingivalis membrane vesicles.
    Methods: Immortalized human gingival epithelial cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP on mRNA expression of cyclooxygenase (COX)-2, interleukin (IL)-6 and -8, and matrix metalloproteinase (MMP)-1 and -3 were examined using real-time reverse transcription-polymerase chain reaction.
    Results: HBP inhibited the mRNA expression of COX-2, IL-6 and -8, and MMP-1 and -3 in a dose-dependent manner, whereas epigallocatechin gallate (a control polyphenol) inhibited COX-2 mRNA expression only. Following further fractionation of HBP to identify the effective components, 2-[(2-methylpropanoyl)-phloroglucinoll 1-O-beta-D-glucopyranoside (MPPG) was identified as a significant anti-inflammatory element that completely inhibited the inflammatory mRNA induction. Kaempferol 3-O-beta-glucopyranoside (astragalin) also was found to have antiinflammatory effects.
    Conclusions: HBP is suggested to be a potent inhibitor of cellular inflammatory responses induced by P. gingivalis vesicles. Further, MPPG and astragalin, identified here as effective components of HBP, also may be useful for the prevention and/or attenuation of periodontitis.

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  • Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols

    Yurong Kou, Hiroaki Inaba, Takahiro Kato, Motoyuki Tagashira, Daiki Honma, Tornornasa Kanda, Yasuyuki Ohtake, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   79 ( 1 )   174 - 180   2008年1月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Periodontitis is induced by an imbalance between bacterial virulence and host defense ability. Porphyromonas gingivalis, a predominant periodontal pathogen, triggers a series of host inflammatory responses that aggravate the destruction of periodontium. Thus, anti-inflammatory reagents are considered desirable for effective periodontal therapy. In the present study, we examined the inhibitory effects of hop bract polyphenol (HBP) on cellular inflammatory responses induced by P. gingivalis membrane vesicles.
    Methods: Immortalized human gingival epithelial cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP on mRNA expression of cyclooxygenase (COX)-2, interleukin (IL)-6 and -8, and matrix metalloproteinase (MMP)-1 and -3 were examined using real-time reverse transcription-polymerase chain reaction.
    Results: HBP inhibited the mRNA expression of COX-2, IL-6 and -8, and MMP-1 and -3 in a dose-dependent manner, whereas epigallocatechin gallate (a control polyphenol) inhibited COX-2 mRNA expression only. Following further fractionation of HBP to identify the effective components, 2-[(2-methylpropanoyl)-phloroglucinoll 1-O-beta-D-glucopyranoside (MPPG) was identified as a significant anti-inflammatory element that completely inhibited the inflammatory mRNA induction. Kaempferol 3-O-beta-glucopyranoside (astragalin) also was found to have antiinflammatory effects.
    Conclusions: HBP is suggested to be a potent inhibitor of cellular inflammatory responses induced by P. gingivalis vesicles. Further, MPPG and astragalin, identified here as effective components of HBP, also may be useful for the prevention and/or attenuation of periodontitis.

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  • Heterogenic virulence and related factors among clinical isolates of Porphyromonas gingivalis with type II fimbriae

    Oral Microbiology and Immunology   23, 29-35   2008年

  • Functional analysis of 51integrin and lipid rafts in invasion of epithelial cells by Porphyromonas gingivlis using fluorescent beads coated with bacterial membrane vesicle

    Cell Structure Function   33 ( 1 )   123 - 132   2008年

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  • ビール・ホップポリフェノールによる歯周炎症の抑制

    天野 敦雄, 稲葉 裕明, 加藤 隆大, 竹内 洋輝, 秋山 茂久, 森崎 市治郎

    障害者歯科 = JOURNAL OF THE JAPANESE SOIETY FOR DISABILITY AND ORAL HEALTH   28 ( 3 )   431 - 431   2007年9月

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  • 歯肉肥大発症因子のDNAマイクロアレイ解析

    加藤 隆大, 稲葉 裕明, 竹内 洋輝, 森崎 市治郎, 天野 敦雄

    障害者歯科 = JOURNAL OF THE JAPANESE SOIETY FOR DISABILITY AND ORAL HEALTH   28 ( 3 )   254 - 254   2007年9月

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  • Detection and serotype distribution of Actinobacillus actinomycetemcomitans in cardiovascular specimens from Japanese patients

    K. Nakano, H. Inaba, R. Nomura, H. Nemoto, K. Tamura, E. Miyamoto, H. Yoshioka, K. Taniguchi, A. Amano, T. Ooshima

    ORAL MICROBIOLOGY AND IMMUNOLOGY   22 ( 2 )   136 - 139   2007年4月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Actinobacillus actinomycetemcomitans, an important pathogen in periodontitis, has also been detected in cardiovascular tissues. Sixty heart valves were collected during valve replacement surgery from 60 patients (one from each), 10 were from patients with infective endocarditis (IE group) and 50 were from patients with other valvular diseases (non-IE group). In addition, 46 samples of aneurysmal tissue were taken from 46 patients with a thoracic or abdominal aneurysm (Aneurysm group, one from each). Dental plaque samples were taken from 54 of the patients, 31 in the IE and non-IE groups and 23 in the aneurysm group. First, the distribution of A. actinomycetemcomitans in all specimens was analysed using a polymerase chain reaction method, which resulted in a positive reaction in 33 (31.1%) of the cardiovascular specimens and 25 (46.3%) of the dental plaque samples. Next, using serotype-specific sets of primers, the serotype distribution of A. actinomycetemcomitans in the cardiovascular specimens and dental plaque samples was found to be significantly different compared to dental plaque samples from Japanese subjects reported previously.

    DOI: 10.1111/j.1399-302X.2007.00332.x

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  • Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype

    Takahiro Kato, Shinji Kawai, Kazuhiko Nakano, Hiroaki Inaba, Masae Kuboniwa, Ichiro Nakagawa, Kayoko Tsuda, Hiroko Omori, Takashi Ooshima, Tamotsu Yoshimori, Atsuo Amano

    CELLULAR MICROBIOLOGY   9 ( 3 )   753 - 765   2007年3月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes based on the diversity of the fimA genes encoding each fimbria subunit. It was suggested that P. gingivalis strains with type II fimbriae were more virulent than type I strains. For the present study, we generated the mutants in which fimA was substituted with different genotypes to study virulence of type II fimbriae. Using plasmid vectors, fimA of ATCC33277 (type I strain) was substituted with type II fimA, and that of OMZ314 (type II strain) with type I fimA. The substitution of type I fimA with type II enhanced bacterial adhesion/invasion to epithelial cells, whereas substitution with type I fimA resulted in diminished efficiency. Following bacterial invasion, type II clones swiftly degraded cellular paxillin and focal adhesion kinase, and inhibited cellular migration, whereas type I clones and Delta fimA mutants did not. BIAcore analysis demonstrated that type II fimbriae possess greater adhesive abilities for their receptor alpha 5 beta 1-integrin than those of type I. In a mouse abscess model, the type II clones significantly induced serum IL-1 beta and IL-6, as well as other infectious symptoms. These results suggest that type II fimbriae are a critical determinant of P. gingivalis virulence.

    DOI: 10.1111/j.1462-5822.2006.00825.x

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  • 線毛遺伝子型の形質転換による Porphyromonas gingivalis 病原性の変化

    加藤 隆大, 稲葉 裕明, 秋山 茂久, 森崎 市治郎, 天野 敦雄

    障害者歯科 = JOURNAL OF THE JAPANESE SOIETY FOR DISABILITY AND ORAL HEALTH   27 ( 3 )   432 - 432   2006年9月

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  • Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens

    Kazuhiko Nakano, Hiroaki Inaba, Ryota Nomura, Hirotoshi Nemoto, Munehiro Takeda, Hideo Yoshioka, Hajime Matsue, Toshiki Takahashi, Kazuhiro Taniguchi, Atsuo Amano, Takashi Ooshima

    JOURNAL OF CLINICAL MICROBIOLOGY   44 ( 9 )   3313 - 3317   2006年9月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    The involvement of oral bacteria in the pathogenesis of cardiovascular diseases has been the focus of attention in many studies, and several periodontal pathogens have been detected in diseased cardiovascular lesions, suggesting relationships between oral microorganisms and cardiovascular diseases. However, no information is available regarding the involvement of cariogenic pathogens such as Streptococcus mutans. The presence of oral streptococcal species and periodontitis-related bacteria in 35 heart valve and 27 atheromatous plaque clinical specimens, as well as 32 dental plaque specimens from the same subjects, was analyzed using a PCR method. Furthermore, broad-range PCR with DNA sequencing analysis was employed to identify the bacterial species in those samples. Streptococcus mutans was frequently detected in the heart valve (69%) and atheromatous plaque (74%) specimens, while other bacterial species, including those related to periodontitis, were detected with much lower frequencies. The bacterial composition in cardiovascular tissues was found to be markedly distinct from that in dental plaque, with only a limited number of species, including S. mutans, in the cardiovascular regions shown to have possibly originated from the oral cavity. Semiquantitative assay results revealed that S. mutans was detected in significant quantities in the heart valve (40%) and atheromatous plaque (48%) specimens, whereas the quantities of all other tested bacterial species, including several related to periodontitis, were negligible in the cardiovascular samples. These results indicate that S. mutans is a possible causative agent of cardiovascular disease.

    DOI: 10.1128/JCM.00377-06

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  • Hop polyphenol prevents inflammatory responses of epithelial cells stimulated with P. gingivalis

    寇 育榮, 稲葉 裕明, 加藤 隆大, 田頭 素行, 本間 大樹, 神田 智正, 大竹 康之, 天野 敦雄

    口腔衛生学会雑誌 = JOURNAL OF DENTAL HEALTH   56 ( 4 )   626 - 626   2006年8月

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  • Invasion of epithelial cells and proteolysis of cellular focal adhesion components by distinct types of Porphyromonas gingivalis fimbriae

    Nakagawa, I, H Inaba, T Yamamura, T Kato, S Kawai, T Oshima, A Amano

    INFECTION AND IMMUNITY   74 ( 7 )   3773 - 3782   2006年7月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Porphyromonas gingivalis fimbriae are classified into six types (types I to V and Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play a critical role in bacterial interactions with host tissues. In this study, we compared the efficiencies of P. gingivalis strains with distinct types of fimbriae for invasion of epithelial cells and for degradation of cellular focal adhesion components, paxillin, and focal adhesion kinase (FAK). Six representative strains with the different types of fimbriae were tested, and P. gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded epithelial cells at significantly greater levels than the other strains. There were negligible differences in gingipain activities among the six strains; however, type II P. gingivalis apparently degraded intracellular paxillin in association with a loss of phosphorylation 30 min after infection. Degradation was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was degraded by the mutant with Lys-gingipain disrupted, and this degradation was prevented by inhibition of Arg-gingipain activity by N alpha-p-tosyl-L-lysine chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular focal adhesions with green fluorescent protein-paxillin macroaggregates were clearly destroyed, and this was associated with cellular morphological changes and microtubule disassembly. In an in vitro wound closure assay, type II P. gingivalis significantly inhibited cellular migration and proliferation compared to the cellular migration and proliferation observed with the other types. These results suggest that type II P. gingivalis efficiently invades epithelial cells and degrades focal adhesion components with Arg-gingipain, which results in cellular impairment during wound healing and periodontal tissue regeneration.

    DOI: 10.1128/IAI.01902-05

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  • Invasion of epithelial cells and proteolysis of cellular focal adhesion components by distinct types of Porphyromonas gingivalis fimbriae

    Nakagawa, I, H Inaba, T Yamamura, T Kato, S Kawai, T Oshima, A Amano

    INFECTION AND IMMUNITY   74 ( 7 )   3773 - 3782   2006年7月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Porphyromonas gingivalis fimbriae are classified into six types (types I to V and Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play a critical role in bacterial interactions with host tissues. In this study, we compared the efficiencies of P. gingivalis strains with distinct types of fimbriae for invasion of epithelial cells and for degradation of cellular focal adhesion components, paxillin, and focal adhesion kinase (FAK). Six representative strains with the different types of fimbriae were tested, and P. gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded epithelial cells at significantly greater levels than the other strains. There were negligible differences in gingipain activities among the six strains; however, type II P. gingivalis apparently degraded intracellular paxillin in association with a loss of phosphorylation 30 min after infection. Degradation was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was degraded by the mutant with Lys-gingipain disrupted, and this degradation was prevented by inhibition of Arg-gingipain activity by N alpha-p-tosyl-L-lysine chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular focal adhesions with green fluorescent protein-paxillin macroaggregates were clearly destroyed, and this was associated with cellular morphological changes and microtubule disassembly. In an in vitro wound closure assay, type II P. gingivalis significantly inhibited cellular migration and proliferation compared to the cellular migration and proliferation observed with the other types. These results suggest that type II P. gingivalis efficiently invades epithelial cells and degrades focal adhesion components with Arg-gingipain, which results in cellular impairment during wound healing and periodontal tissue regeneration.

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  • Inhibitory effects of tumor necrosis factor-α on migration of human periodontal ligament cells

    Journal of Periodontology   77 ( 5 )   883 - 890   2006年5月

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  • Inhibitory effects of tumor necrosis factor-alpha on migration of human periodontal ligament cells

    Akane Takemura, Ichiro Nakagawa, Shinji Kawai, Hiroaki Inaba, Takahiro Kato, Shigeyuki Hamada, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   77 ( 5 )   883 - 890   2006年5月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Tumor necrosis factor-alpha (TNF-alpha) is associated with chronic gingival inflammation and is suspected to influence periodontal destruction. However, the exact roles of TNF-alpha in wound healing and periodontal tissue regeneration are largely unknown. In the present study, we examined the effects of TNF-alpha on migration and proliferation of human periodontal ligament (PDL) cells.
    Methods: PDL cells were cultured in the presence of TNF-alpha to determine its effects on cellular migration and proliferation. The protein expression profiles of alpha 5 and beta 1 integrin subunits and their related molecules, paxillin and focal adhesion kinases (FAK), were investigated. Gene expression of fibronectin also was assayed. Further, the activation of Rho-family small guanosine triphosphate (GTP)-binding protein (RhoA) was evaluated using a GTP-loading pull-down assay, and focal adhesion formation by PDL cells after transfection with the expression vector of paxillin-fused green fluorescent protein (GFP) also was observed with confocal microscopy.
    Results: Cellular migration was impaired by TNF-a and recovered following the addition of anti-TNF-alpha antibodies. In contrast, PDL cell proliferation was not affected by TNF-alpha. TNF-alpha upregulated the expression of the alpha 5 and beta 1 integrin subunits, whereas fibronectin was not overexpressed. Phosphorylation of paxillin and FAK by PDL cells was induced, and RhoA activation also was induced. Confocal microscopic analysis revealed that TNF-alpha induced focal adhesion and stress fiber formation in all parts of the cells.
    Conclusion: Our results suggested that TNF-alpha impairs cellular migration by enhancing cellular adhesive ability following significant focal adhesion and stress fiber formation.

    DOI: 10.1902/jop.2006.050192

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  • Proinflammatory gene expression in mouse ST2 cell line in response to infection by Porphyromonas gingivalis

    T Ohno, N Okahashi, S Kawai, T Kato, H Inaba, Y Shibata, Morisaki, I, Y Abiko, A Amano

    MICROBES AND INFECTION   8 ( 4 )   1025 - 1034   2006年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Porphyromonas gingivalis is a predominant periodontal pathogen, whose infection causes inflammatory responses in periodontal tissue and alveolar bone resorption. Various virulence factors of this pathogen modulate host innate immune responses. It has been reported that gingipains degrade a wide variety of host cell proteins, and fimbriae are involved in bacterial adhesion to and invasion of host cells. In the present study, we profiled ST2 stromal cell gene expression following infection with the viable P. gingivalis strain ATCC33277 as well as with its gingipain- and fimbriae-deficient mutants, using microarray technology and quantitative real-time polymerase chain reaction. Using a mouse array of about 20,000 genes, we found that infection with the wild strain elicited a significant upregulation (greater than 2-fold) of expression of about 360 genes in ST2 cells, which included the chemokines CCL2, CCL5, and CXCL10, and other proinflammatory proteins such as interleukin-6 (IL-6) and matrix metalloproteinase-13 (MMP-13). Further, infection with the gingipain-deficient mutant elicited a reduced expression of the CXCL10, IL-6 and MMP-13 genes, suggesting that gingipains play an important role in inducing the expression of those genes following P. gingivalis infection. On the other hand, the pattern of global gene expression induced by the fimbriae-deficient mutant was similar to that by the wild strain. These results suggest that P. gingivalis infection induces gene expression of a wide variety of proinflammatory proteins in stromal cells/osteoblasts, and gingipains may be involved in inducing several of the proinflammatory factors. (c) 2005 Elsevier SAS. All rights reserved.

    DOI: 10.1016/j.micinf.2005.10.021

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  • Proinflammatory gene expression in mouse ST2 cell line in response to infection by Porphyromonas gingivalis

    T Ohno, N Okahashi, S Kawai, T Kato, H Inaba, Y Shibata, Morisaki, I, Y Abiko, A Amano

    MICROBES AND INFECTION   8 ( 4 )   1025 - 1034   2006年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Porphyromonas gingivalis is a predominant periodontal pathogen, whose infection causes inflammatory responses in periodontal tissue and alveolar bone resorption. Various virulence factors of this pathogen modulate host innate immune responses. It has been reported that gingipains degrade a wide variety of host cell proteins, and fimbriae are involved in bacterial adhesion to and invasion of host cells. In the present study, we profiled ST2 stromal cell gene expression following infection with the viable P. gingivalis strain ATCC33277 as well as with its gingipain- and fimbriae-deficient mutants, using microarray technology and quantitative real-time polymerase chain reaction. Using a mouse array of about 20,000 genes, we found that infection with the wild strain elicited a significant upregulation (greater than 2-fold) of expression of about 360 genes in ST2 cells, which included the chemokines CCL2, CCL5, and CXCL10, and other proinflammatory proteins such as interleukin-6 (IL-6) and matrix metalloproteinase-13 (MMP-13). Further, infection with the gingipain-deficient mutant elicited a reduced expression of the CXCL10, IL-6 and MMP-13 genes, suggesting that gingipains play an important role in inducing the expression of those genes following P. gingivalis infection. On the other hand, the pattern of global gene expression induced by the fimbriae-deficient mutant was similar to that by the wild strain. These results suggest that P. gingivalis infection induces gene expression of a wide variety of proinflammatory proteins in stromal cells/osteoblasts, and gingipains may be involved in inducing several of the proinflammatory factors. (c) 2005 Elsevier SAS. All rights reserved.

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  • Effect of phenytoin on collagen accumulation by human gingival fibroblasts exposed to TNF-alpha in vitro

    T Kato, N Okahashi, T Ohno, H Inaba, S Kawai, A Amano

    ORAL DISEASES   12 ( 2 )   156 - 162   2006年3月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    OBJECTIVE: Tumor necrosis factor (TNF)-alpha is associated with chronic gingival inflammation and reported to induce gingival overgrowth (GO), while phenytoin (PHT) is also known to be a causative agent of GO. We examined the synergistic effect of PHT and TNF-alpha on collagen metabolism in human gingival fibroblasts (HGFs).
    MATERIALS AND METHODS: HGFs were cultured with TNF-alpha and PHT. Quantitative real-time RT-PCR was employed to determine the mRNA levels for collagen, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and integrin subunits. Cellular collagen endocytosis was determined using a flow-cytometry.
    RESULTS: The proliferation of HGFs was not affected by TNF-alpha or PHT individually, whereas both synergistically increased collagen accumulation in HGFs. Further, collagen mRNA expression was not increased by TNF-alpha or PHT, although together they markedly prevented cellular collagen endocytosis, associated with the suppression of alpha 2 beta 1-integrin mRNA expression. The mRNA expression of MMP-1 and-2 was suppressed by PHT, while TIMP-1 mRNA expression was enhanced by both TNF-alpha and PHT.
    CONCLUSION: Our results suggest that TNF-alpha and PHT together cause impaired collagen metabolism by suppression of enzymatic degradation with MMPs/TIMP-1 and integrin-mediated endocytosis. These synergistic effects may also be involved in TNF-alpha- and PHT-induced collagen accumulation, leading to GO.

    DOI: 10.1111/j.1601-0825.2005.01175.x

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  • Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients

    Munehiro Takeda, Miki Ojima, Hideo Yoshioka, Hiroaki Inaba, Mikihiko Kogo, Satoshi Shizukuishi, Makoto Nomura, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   77 ( 1 )   15 - 20   2006年1月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: A close relationship between diabetes and chronic periodontitis has been demonstrated. We previously found that Porphyromonas gingivalis with the type II fimA gene is an infectious factor closely associated with the deterioration seen in diabetic periodontitis patients. In the present study, we examined whether other biomarkers are related to the development and deterioration of periodontitis often seen in type 2 diabetic individuals.
    Methods: A total of 97 type 2 diabetes patients with and without periodontitis were recruited, and their periodontal and diabetic conditions were analyzed. The ratio (%) of teeth with an attachment loss &gt; 5 mm among all teeth in each subject was used as an index of periodontal deterioration. Peripheral blood was tested for levels of glycated hemoglobin (HbA1c), advanced glycation end products (AGES), C-reactive protein (CRP), and cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1 beta. Subgingival plaque samples were also examined for the occurrences of Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia.
    Results: Serum AGES were significantly associated with deterioration of periodontitis, whereas no other serum biochemical marker or bacterial occurrence showed a clear relationship with that condition.
    Conclusion: AGES may be factors associated with diabetic periodontitis and may be useful as biomarkers that reflect such deterioration.

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  • Association between epithelial cell death and invasion by microspheres conjugated to Porphyromonas gingivalis vesicles with different types of fimbriae

    H Inaba, S Kawai, T Kato, Nakagawa, I, A Amano

    INFECTION AND IMMUNITY   74 ( 1 )   734 - 739   2006年1月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Microspheres (MS) conjugated to Porphyromonas gingivalis vesicles with type 11 fimbriae were the most efficient human epithelial cell invaders among the six types. Cell death was induced by MS, though becoming less frequent over time, with invasion efficiency partially related to cell death and gingipains likely the major cause.

    DOI: 10.1128/IAI.74.1.734-739.2006

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  • Association between epithelial cell death and invasion by microspheres conjugated to Porphyromonas gingivalis vesicles with different types of fimbriae

    H Inaba, S Kawai, T Kato, Nakagawa, I, A Amano

    INFECTION AND IMMUNITY   74 ( 1 )   734 - 739   2006年1月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Microspheres (MS) conjugated to Porphyromonas gingivalis vesicles with type 11 fimbriae were the most efficient human epithelial cell invaders among the six types. Cell death was induced by MS, though becoming less frequent over time, with invasion efficiency partially related to cell death and gingipains likely the major cause.

    DOI: 10.1128/IAI.74.1.734-739.2006

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  • Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients

    Munehiro Takeda, Miki Ojima, Hideo Yoshioka, Hiroaki Inaba, Mikihiko Kogo, Satoshi Shizukuishi, Makoto Nomura, Atsuo Amano

    JOURNAL OF PERIODONTOLOGY   77 ( 1 )   15 - 20   2006年1月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: A close relationship between diabetes and chronic periodontitis has been demonstrated. We previously found that Porphyromonas gingivalis with the type II fimA gene is an infectious factor closely associated with the deterioration seen in diabetic periodontitis patients. In the present study, we examined whether other biomarkers are related to the development and deterioration of periodontitis often seen in type 2 diabetic individuals.
    Methods: A total of 97 type 2 diabetes patients with and without periodontitis were recruited, and their periodontal and diabetic conditions were analyzed. The ratio (%) of teeth with an attachment loss &gt; 5 mm among all teeth in each subject was used as an index of periodontal deterioration. Peripheral blood was tested for levels of glycated hemoglobin (HbA1c), advanced glycation end products (AGES), C-reactive protein (CRP), and cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1 beta. Subgingival plaque samples were also examined for the occurrences of Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia.
    Results: Serum AGES were significantly associated with deterioration of periodontitis, whereas no other serum biochemical marker or bacterial occurrence showed a clear relationship with that condition.
    Conclusion: AGES may be factors associated with diabetic periodontitis and may be useful as biomarkers that reflect such deterioration.

    DOI: 10.1902/jop.2006.77.1.15

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  • Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis

    H Inaba, M Tagashira, T Kanda, T Ohno, S Kawai, A Amano

    JOURNAL OF PERIODONTOLOGY   76 ( 12 )   2223 - 2229   2005年12月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Enamel matrix derivative (EMD) is a tissue regenerative agent used clinically as an adjunct to periodontal surgery. It was previously demonstrated that Porphyromonas gingivalis, a periodontal pathogen, significantly diminished the efficacy of EMD with periodontal ligament (PDL) cells through the proteolytic actions of Arg- and Lys-gingipains (Rgp and Kgp). Thus, antiproteolytic supplements are considered clinically desirable for effective periodontal regenerative therapies. In the present study, we examined apple- (AP) and hop-polyphenols to determine their ability to protect EMD-stimulated PDL cells from P. gingivalis.
    Methods: AP, apple condensed tannin (ACT), hop bract polyphenol (HBP), high and low molecular weight fractions of HBP (HMW-HBP and LMW-HBP), and epigallocatechin gallate (EGCg) were used. PDL cells were grown on EMD-coated dishes and infected with P. gingivalis, and cellular migration and proliferation were evaluated with an in vitro assay of wound healing assay in the presence or absence of the polyphenols.
    Results: Each polyphenol significantly enhanced the viability of PDL cells infected with P. gingivalis, whereas only EGCg demonstrated cytotoxicity. Further, all polyphenols significantly inhibited Rgp activity, with AP, ACT, and HBP more effective toward Kgp. P. gingivalis markedly diminished the migration and proliferation of EMD-stimulated PDL cells, whereas the addition of AP, ACT, HBP, and HMW-HBP significantly protected the cells from bacterial cytotoxicity. In contrast, EGCg and LMW-HBP did not show protective effects.
    Conclusion: These results suggest that AP, ACT, AP, HBP, and HMW-HBP protect EMD-stimulated PDL cells from P. gingivalis and may be therapeutically useful supplements for EMD therapy.

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  • Molecular dissection of internalization of Porphyromonas gingivalis by cells using fluorescent beads coated with bacterial membrane vesicle

    K Tsuda, A Amano, K Umebayashi, H Inaba, Nakagawa, I, Y Nakanishi, T Yoshimori

    CELL STRUCTURE AND FUNCTION   30 ( 1-2 )   81 - 91   2005年12月

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    記述言語:英語   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Porphyromonas gingivalis is one of the causative agents of adult periodontitis, and has been reported to be internalized by nonphagocytic epithelial cells. However, the mechanism for the internalization remains unclear. In the present study, we addressed this issue using fluorescent beads coated with bacterial membrane vesicles (MVs) that retain surface components of P. gingivalis. We established an assay system in which we could easily quantify the bead internalization to cells. MVs-coated beads were internalized by HeLa cells in kinetics similar to that of living bacteria. The internalization depended on dynamin but not clathrin. The beads were internalized through the actin-mediated pathway that is controlled by phosphatidylinositol (PI) 3-kinase. The dynamics of microtubule assembly and disassembly was also required. Further, the treatment of cells with cholesterol-binding reagents significantly inhibited bead internalization, and the internalized beads were apparently colocalized with ganglioside GM1 and caveolin-1, which suggest the involvement of the lipid raft in the process. These results suggest that P. gingivalis accomplishes its internalization utilizing membrane lipid raft and cytoskeletal functions of the target cells.

    DOI: 10.1247/csf.30.81

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  • Molecular dissection of internalization of Porphyromonas gingivalis by cells using fluorescent beads coated with bacterial membrane vesicle

    K Tsuda, A Amano, K Umebayashi, H Inaba, Nakagawa, I, Y Nakanishi, T Yoshimori

    CELL STRUCTURE AND FUNCTION   30 ( 1-2 )   81 - 91   2005年12月

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    記述言語:英語   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Porphyromonas gingivalis is one of the causative agents of adult periodontitis, and has been reported to be internalized by nonphagocytic epithelial cells. However, the mechanism for the internalization remains unclear. In the present study, we addressed this issue using fluorescent beads coated with bacterial membrane vesicles (MVs) that retain surface components of P. gingivalis. We established an assay system in which we could easily quantify the bead internalization to cells. MVs-coated beads were internalized by HeLa cells in kinetics similar to that of living bacteria. The internalization depended on dynamin but not clathrin. The beads were internalized through the actin-mediated pathway that is controlled by phosphatidylinositol (PI) 3-kinase. The dynamics of microtubule assembly and disassembly was also required. Further, the treatment of cells with cholesterol-binding reagents significantly inhibited bead internalization, and the internalized beads were apparently colocalized with ganglioside GM1 and caveolin-1, which suggest the involvement of the lipid raft in the process. These results suggest that P. gingivalis accomplishes its internalization utilizing membrane lipid raft and cytoskeletal functions of the target cells.

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  • Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis

    H Inaba, M Tagashira, T Kanda, T Ohno, S Kawai, A Amano

    JOURNAL OF PERIODONTOLOGY   76 ( 12 )   2223 - 2229   2005年12月

     詳細を見る

    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Enamel matrix derivative (EMD) is a tissue regenerative agent used clinically as an adjunct to periodontal surgery. It was previously demonstrated that Porphyromonas gingivalis, a periodontal pathogen, significantly diminished the efficacy of EMD with periodontal ligament (PDL) cells through the proteolytic actions of Arg- and Lys-gingipains (Rgp and Kgp). Thus, antiproteolytic supplements are considered clinically desirable for effective periodontal regenerative therapies. In the present study, we examined apple- (AP) and hop-polyphenols to determine their ability to protect EMD-stimulated PDL cells from P. gingivalis.
    Methods: AP, apple condensed tannin (ACT), hop bract polyphenol (HBP), high and low molecular weight fractions of HBP (HMW-HBP and LMW-HBP), and epigallocatechin gallate (EGCg) were used. PDL cells were grown on EMD-coated dishes and infected with P. gingivalis, and cellular migration and proliferation were evaluated with an in vitro assay of wound healing assay in the presence or absence of the polyphenols.
    Results: Each polyphenol significantly enhanced the viability of PDL cells infected with P. gingivalis, whereas only EGCg demonstrated cytotoxicity. Further, all polyphenols significantly inhibited Rgp activity, with AP, ACT, and HBP more effective toward Kgp. P. gingivalis markedly diminished the migration and proliferation of EMD-stimulated PDL cells, whereas the addition of AP, ACT, HBP, and HMW-HBP significantly protected the cells from bacterial cytotoxicity. In contrast, EGCg and LMW-HBP did not show protective effects.
    Conclusion: These results suggest that AP, ACT, AP, HBP, and HMW-HBP protect EMD-stimulated PDL cells from P. gingivalis and may be therapeutically useful supplements for EMD therapy.

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  • Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin

    Takahiro Kato, Nobuo Okahashi, Shinji Kawai, Takafumi Kato, Hiroaki Inaba, Ichijiro Morisaki, Atsuo Amano

    Journal of Periodontology   76 ( 6 )   941 - 950   2005年6月

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    記述言語:英語  

    Background: Gingival overgrowth (GO) is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced GO characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF). Methods: HGFs were cultured with various concentrations of PHT and viable cell numbers and collagen amounts were determined. Gene and protein expressions of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) were quantified with reverse transcription-polymerase chain reaction (RT-PCR) analyses and Western blotting, respectively. Cellular endocytosis of collagen was assayed using flow-cytometric analysis. The effects of PHT on extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibitor κB-α (IκB-α) were assayed. Results: The proliferation of HGFs was not affected by PHT, whereas it significantly increased collagen accumulation. Further, the expressions of MMP-1, -2, and -3 were markedly suppressed by PHT, whereas that of TIMP-1 was induced in a dose- and time-dependent manner. PHT also markedly prevented collagen endocytosis by HGFs, which was associated with the suppression of α2β1-integrin expression. In addition, the phosphorylation of ERK1/2 and IκB-α degradation were suppressed by PHT. Conclusions: These results suggest that PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and α2β1-integrin-mediated endocytosis. Those alterations are likely mediated through the cellular signaling pathways of ERK1/2 and nuclear factor κB. These synergistic effects may cause collagen accumulation, leading to GO.

    DOI: 10.1902/jop.2005.76.6.941

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  • Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin

    T Kato, N Okahashi, S Kawai, T Kato, H Inaba, Morisaki, I, A Amano

    JOURNAL OF PERIODONTOLOGY   76 ( 6 )   941 - 950   2005年6月

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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Gingival overgrowth (GO) is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced GO characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the Collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF).
    Methods: HGFs were cultured with various concentrations of PHT and viable cell numbers and collagen amounts were determined. Gene and protein expressions of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) were quantified with reverse transcription-polymerase chain reaction (RT-PCR) analyses and Western blotting, respectively. Cellular endocytosis of collagen was assayed using flow-cytometric analysis. The effects of PHT on extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibitor kappa B-alpha (I kappa B-alpha) were assayed.
    Results: The proliferation of HGFs was not affected by PHT, whereas it significantly increased collagen accumulation. Further, the expressions of MMP- 1, -2, and -3 were markedly suppressed by PHT, whereas that of TIMP-1 was induced in a dose- and time-dependent manner. PHT also markedly prevented Collagen endocytosis by HGFs, which was associated with the suppression of alpha 2 beta 1-integrin expression. In addition, the phosphorylation of ERK1/2 and I kappa B-alpha degradation were suppressed by PHT.
    Conclusions: These results suggest that PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and alpha 2 beta 1-integrin-mediated endocytosis. Those alterations are likely mediated through the cellular signaling pathways of ERK1/2 and nuclear factor kappa B. These synergistic effects may cause collagen accumulation, leading to GO.

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  • Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin

    Takahiro Kato, Nobuo Okahashi, Shinji Kawai, Takafumi Kato, Hiroaki Inaba, Ichijiro Morisaki, Atsuo Amano

    Journal of Periodontology   76 ( 6 )   941 - 950   2005年6月

     詳細を見る

    記述言語:英語  

    Background: Gingival overgrowth (GO) is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced GO characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF). Methods: HGFs were cultured with various concentrations of PHT and viable cell numbers and collagen amounts were determined. Gene and protein expressions of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) were quantified with reverse transcription-polymerase chain reaction (RT-PCR) analyses and Western blotting, respectively. Cellular endocytosis of collagen was assayed using flow-cytometric analysis. The effects of PHT on extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibitor κB-α (IκB-α) were assayed. Results: The proliferation of HGFs was not affected by PHT, whereas it significantly increased collagen accumulation. Further, the expressions of MMP-1, -2, and -3 were markedly suppressed by PHT, whereas that of TIMP-1 was induced in a dose- and time-dependent manner. PHT also markedly prevented collagen endocytosis by HGFs, which was associated with the suppression of α2β1-integrin expression. In addition, the phosphorylation of ERK1/2 and IκB-α degradation were suppressed by PHT. Conclusions: These results suggest that PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and α2β1-integrin-mediated endocytosis. Those alterations are likely mediated through the cellular signaling pathways of ERK1/2 and nuclear factor κB. These synergistic effects may cause collagen accumulation, leading to GO.

    DOI: 10.1902/jop.2005.76.6.941

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  • Odd-skipped related 2 splicing variants show opposite transcriptional activity

    Shinji Kawai, Takahiro Kato, Hiroaki Inaba, Nobuo Okahashi, Atsuo Amano

    Biochemical and Biophysical Research Communications   328 ( 1 )   306 - 311   2005年3月

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    記述言語:英語  

    Odd-skipped related 2 (Osr2) is expressed in the domain of epithelial-mesenchymal interactions during tooth and kidney development. In this study, we report that alternative splicing of exon 4 resulted in two transcripts, Osr2A and Osr2B. These variants utilized a different splice acceptor, and Osr2B exhibited a frameshift followed by an early stop codon. Osr2A mRNA produced a protein that was 36 amino acids longer than Osr2B at the C-terminus and had five zinc-finger domains, whereas Osr2B had three zinc-finger motives. The 2 Osr2 variants were found in kidney, skeletal muscle, and testis, and Osr2B was predominantly transcribed in each. Flag-tagged variants showed the same localization in cell nuclei, however, Gal4 fusion proteins showed opposite transcriptional activities. Further, Flag-tagged variants also showed opposite transcriptional activities, though they were in contrast to the findings for the Gal4-fused variants. Our results indicate that Osr2 bifurcates its function by alternative splicing. © 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.12.173

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  • Odd-skipped related 2 splicing variants show opposite transcriptional activity

    S Kawai, T Kato, H Inaba, N Okahashi, A Amano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   328 ( 1 )   306 - 311   2005年3月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Odd-skipped related 2 (Osr2) is expressed in the domain of epithelial-mesenchymal interactions during tooth and kidney development. In this study, we report that alternative splicing of exon 4 resulted in two transcripts, Osr2A and Osr2B. These variants utilized a different splice acceptor, and Osr2B exhibited a frameshift followed by an early stop codon. Osr2A mRNA produced a protein that was 36 amino acids longer than Osr2B at the C-terminus and had five zinc-finger domains, whereas Osr2B had three zinc-finger motives. The 2 Osr2 variants were found in kidney, skeletal muscle, and testis, and Osr2B was predominantly transcribed in each. Flag-tagged variants showed the same localization in cell nuclei, however, Ga14 fusion proteins showed opposite transcriptional activities. Further, Flag-tagged variants also showed opposite transcriptional activities, though they were in contrast to the findings for the Ga14-fused variants. Our results indicate that Osr2 bifurcates its function by alternative splicing. (C) 2005 Elsevier Inc. All rights reserved.

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  • Odd-skipped related 2 splicing variants show opposite transcriptional activity

    S Kawai, T Kato, H Inaba, N Okahashi, A Amano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   328 ( 1 )   306 - 311   2005年3月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Odd-skipped related 2 (Osr2) is expressed in the domain of epithelial-mesenchymal interactions during tooth and kidney development. In this study, we report that alternative splicing of exon 4 resulted in two transcripts, Osr2A and Osr2B. These variants utilized a different splice acceptor, and Osr2B exhibited a frameshift followed by an early stop codon. Osr2A mRNA produced a protein that was 36 amino acids longer than Osr2B at the C-terminus and had five zinc-finger domains, whereas Osr2B had three zinc-finger motives. The 2 Osr2 variants were found in kidney, skeletal muscle, and testis, and Osr2B was predominantly transcribed in each. Flag-tagged variants showed the same localization in cell nuclei, however, Ga14 fusion proteins showed opposite transcriptional activities. Further, Flag-tagged variants also showed opposite transcriptional activities, though they were in contrast to the findings for the Ga14-fused variants. Our results indicate that Osr2 bifurcates its function by alternative splicing. (C) 2005 Elsevier Inc. All rights reserved.

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  • Inhibitory effects of Porphyromonas gingivalis timbriae on interactions between extracellular matrix proteins and cellular integrins

    Nakagawa, I, A Amano, H Inaba, S Kawai, S Hamada

    MICROBES AND INFECTION   7 ( 2 )   157 - 163   2005年2月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Porphvronzonas gingivalis is a predominant periodontal pathogen, whose fimbriae are considered to be a major virulence factor. especially for bacterial adherence and invasion of host cells. In the present study, we investigated the influence of fimbriae on the interactions between alpha v beta 3 and alpha 5 beta 1-integrins and their ligand extracellular matrix (ECM) proteins (vitronectin and fibronectin), using human alpha v beta 3- and alpha 5 beta 1-1-integrin-overexpressing CHO cell lines (CHO alpha v beta 3 and CHO alpha 5 beta 1, respectively). P. gingivalis was found to have significantly greater binding to CHO alpha v beta 3 and CHO alpha 5 beta 1 than to control cells, whereas a fimbria-deficient mutant showed negligible binding to any of the tested cell lines. CHO alpha v beta 3 and CHO alpha 5 beta 1 cells attached to the polystyrene culture dishes in the presence of their ligand ECM proteins, while fimbriae markedly inhibited those attachments in a dose-dependent manner, with the highest dose of fimbriae achieving complete inhibition. In addition, the binding of vitronectin and fibronectin to CHO alpha v beta 3 and CHO alpha 5 beta 1 was inhibited by P. gingivalis cells. These results Suggest that P. gingivalis fimbriae compete with ECM proteins for alpha v beta 3- and alpha 5 beta 1-integrins, and inhibit integrin/ECM protein-related cellular functions. (c) 2005 Elsevier SAS. All rights reserved.

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  • 先端歯科医学の創生「歯周病細菌の細胞傷害戦略」

    大阪大学出版会   2005年

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  • Effect of phenytoin on collagen accumulation by human gingival fibroblasts exposed to TNF-a in vitro.

    Oral Diseases   11巻1-7頁   2005年

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  • Inhibitory effect of Porphyromonas gingivalis fimbriae on interaction between extracellular matrix proteins and cellular integrins.

    Microbes and Infection   7巻2号157-163頁   2005年

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  • C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells

    K Ohnishi, H Inaba, J Yasumoto, K Yuki, A Takahashi, T Ohnishi

    APOPTOSIS   9 ( 5 )   591 - 597   2004年9月

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    記述言語:英語   出版者・発行元:KLUWER ACADEMIC PUBL  

    We propose here a novel p53-targeting radio-cancer therapy using p53 C-terminal peptides for patients having mutated p53. Hoechst 33342 staining showed that X-ray irradiation alone efficiently induced apoptotic bodies in wild-type p53 (wtp53) human head and neck cancer cells transfected with a neo control vector (SAS/neo cells), but hardly induced apoptotic bodies in mutation-type p53 (mp53) cells transfected with a vector carrying the mp53 gene (SAS/mp53). In contrast, transfection of p53 C-terminal peptides (amino acid residues 361-382 or 353-374) via liposomes caused a remarkable increase of apoptotic bodies in X-ray-irradiated SAS/mp53 cells, but did not enhance apoptotic bodies in X-ray-irradiated SAS/neo cells. In immunocytochemical analysis, positively stained cells for active type caspase-3 were observed at high frequency after X-ray irradiation in the SAS/mp53 cells pretreated with p53 C-terminal peptides. In SAS/neo cells, positively stained cells for active type caspase-3 were observed with X-ray irradiation alone. Furthermore, protein extracts from X-ray-irradiated SAS/mp53 cells showed higher DNA-binding activity of p53 to p53 consensus sequence when supplemented in vitro with p53 C-terminal peptides than extracts from non-irradiated SAS/mp53 cells. These results suggest that radiation treatment in the presence of p53 C-terminal peptides is more effective for inducing p53-mediated apoptosis than radiation treatment alone or p53 C-terminal peptide treatment alone, especially in mp53 cancer cells. This novel tool for enhancement of apoptosis induction in mp53 cells might be useful for p53-targeted radio-cancer therapy.

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  • C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells

    K Ohnishi, H Inaba, J Yasumoto, K Yuki, A Takahashi, T Ohnishi

    APOPTOSIS   9 ( 5 )   591 - 597   2004年9月

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    記述言語:英語   出版者・発行元:KLUWER ACADEMIC PUBL  

    We propose here a novel p53-targeting radio-cancer therapy using p53 C-terminal peptides for patients having mutated p53. Hoechst 33342 staining showed that X-ray irradiation alone efficiently induced apoptotic bodies in wild-type p53 (wtp53) human head and neck cancer cells transfected with a neo control vector (SAS/neo cells), but hardly induced apoptotic bodies in mutation-type p53 (mp53) cells transfected with a vector carrying the mp53 gene (SAS/mp53). In contrast, transfection of p53 C-terminal peptides (amino acid residues 361-382 or 353-374) via liposomes caused a remarkable increase of apoptotic bodies in X-ray-irradiated SAS/mp53 cells, but did not enhance apoptotic bodies in X-ray-irradiated SAS/neo cells. In immunocytochemical analysis, positively stained cells for active type caspase-3 were observed at high frequency after X-ray irradiation in the SAS/mp53 cells pretreated with p53 C-terminal peptides. In SAS/neo cells, positively stained cells for active type caspase-3 were observed with X-ray irradiation alone. Furthermore, protein extracts from X-ray-irradiated SAS/mp53 cells showed higher DNA-binding activity of p53 to p53 consensus sequence when supplemented in vitro with p53 C-terminal peptides than extracts from non-irradiated SAS/mp53 cells. These results suggest that radiation treatment in the presence of p53 C-terminal peptides is more effective for inducing p53-mediated apoptosis than radiation treatment alone or p53 C-terminal peptide treatment alone, especially in mp53 cancer cells. This novel tool for enhancement of apoptosis induction in mp53 cells might be useful for p53-targeted radio-cancer therapy.

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  • C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells

    K Ohnishi, H Inaba, J Yasumoto, K Yuki, A Takahashi, T Ohnishi

    APOPTOSIS   9 ( 5 )   591 - 597   2004年9月

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    記述言語:英語   出版者・発行元:KLUWER ACADEMIC PUBL  

    We propose here a novel p53-targeting radio-cancer therapy using p53 C-terminal peptides for patients having mutated p53. Hoechst 33342 staining showed that X-ray irradiation alone efficiently induced apoptotic bodies in wild-type p53 (wtp53) human head and neck cancer cells transfected with a neo control vector (SAS/neo cells), but hardly induced apoptotic bodies in mutation-type p53 (mp53) cells transfected with a vector carrying the mp53 gene (SAS/mp53). In contrast, transfection of p53 C-terminal peptides (amino acid residues 361-382 or 353-374) via liposomes caused a remarkable increase of apoptotic bodies in X-ray-irradiated SAS/mp53 cells, but did not enhance apoptotic bodies in X-ray-irradiated SAS/neo cells. In immunocytochemical analysis, positively stained cells for active type caspase-3 were observed at high frequency after X-ray irradiation in the SAS/mp53 cells pretreated with p53 C-terminal peptides. In SAS/neo cells, positively stained cells for active type caspase-3 were observed with X-ray irradiation alone. Furthermore, protein extracts from X-ray-irradiated SAS/mp53 cells showed higher DNA-binding activity of p53 to p53 consensus sequence when supplemented in vitro with p53 C-terminal peptides than extracts from non-irradiated SAS/mp53 cells. These results suggest that radiation treatment in the presence of p53 C-terminal peptides is more effective for inducing p53-mediated apoptosis than radiation treatment alone or p53 C-terminal peptide treatment alone, especially in mp53 cancer cells. This novel tool for enhancement of apoptosis induction in mp53 cells might be useful for p53-targeted radio-cancer therapy.

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  • Porphyromonas gingivalis Induces Receptor Activator of NF-B Ligand Expression in Osteoblasts through the Activator Protein 1 Pathway

    Infection and Immunity   72 ( 3 )   1706 - 1714   2004年3月

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  • 2型糖尿病に合併する歯周炎の発症・進行に関連する因子

    天野 敦雄, 秋山 茂久, 村上 旬平, 稲葉 裕明, 森崎 市治郎

    障害者歯科   25 ( 3 )   335 - 335   2004年

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    記述言語:日本語   出版者・発行元:(一社)日本障害者歯科学会  

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  • Effect of Enamel Matrix Derivative on Periodontal Ligament Cells in vitro is Diminished by Porphyromonas gingivalis

    J. Periodontol., 75, 858-865.   75, 858-865   2004年

  • Effect of Enamel Matrix Derivative on Periodontal Ligament Cells in vitro is diminished by Porphyromonas gingivalis

    J. Periodontology   75巻6号858-865頁   2004年

  • Effect of Enamel Matrix Derivative on Periodontal Ligament Cells in vitro is Diminished by Porphyromonas gingivalis

    J. Periodontol., 75, 858-865.   75, 858-865   2004年

  • The rgulation of Odd-skipped related gene expression by C/EBPdelta

    2004年

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  • 転写因子C/EBPdeltaによるOdd-skipped related 2遺伝子の発現制御

    2004年

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  • P-gingivalis induces receptor activator of NF-kappa B ligand expression in osteoblasts through AP-1 pathway

    N Okahashi, H Inaba, Nakagaawa, I, K Nakayama, A Amano

    JOURNAL OF DENTAL RESEARCH   82   433 - 433   2003年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Web of Science

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  • Porphyromonas gingivalis の線毛遺伝子多型と病原性との関連

    天野 敦雄, 久保庭 雅恵, 加藤 隆大, 稲葉 裕明

    口腔衛生学会雑誌   53 ( 4 )   358 - 358   2003年8月

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  • Painless mass of the cheek

    H Inaba, Y Ohnishi, M Inaba, H Niki, Y Yamasaki, S Morita, K Kakudo

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS   95 ( 1 )   3 - 6   2003年1月

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    記述言語:英語   出版者・発行元:MOSBY, INC  

    DOI: 10.1067/moe.2003.26

    Web of Science

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  • Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    A Takahashi, N Kondo, H Inaba, K Uotani, Y Kiyohara, K Ohnishi, T Ohnishi

    SPACE LIFE SCIENCES: BIODOSIMETRY, BIOMARKERS AND LATE STOCHASTIC EFFECTS OF SPACE RADIATION   31 ( 6 )   1569 - 1573   2003年

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein-mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr(+)/(+)) were irradiated with X-ray at 3.0 Gy at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunchistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method. The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr(+)/(+) mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews. (C) 2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0273-1177(03)00093-0

    Web of Science

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  • ダウン症患者の歯肉上皮細胞への歯周病原菌の侵入

    村上 旬平, 天野 敦雄, 木村 敬次, 加藤 隆大, 稲葉 裕明, 高田 勇之介, 森崎 市治郎

    障害者歯科   23 ( 3 )   389 - 389   2002年9月

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  • Keratin 19 in benign amelo-blastoma and malignant ameloblastoma ミ immunohistologicalchemistry, reverse transcription-polymerase chain reaction and Northern blot analysis -

    Inaba Hiroaki, Ohnishi Yuichi, Nozaki Masami, Katsuko Horii, Shinichiro Hiraki, Yoshihiro TANAKA, Shosuke MORITA, Kenji KAKUDO, Second Department of Oral and Maxillofacial Surgery Osak Dental University:Department of Science for Laboratory Animal Experimentation Reaearch Institute for Microbial Disease Osaka University, Second Department of Oral and Maxillofacial Surgery Osak Dental University, Department of Science for Laboratory Animal Experimentation Reaearch Institute for Microbial Disease Osaka University, Second Department of Oral and Maxillofacial Surgery Osak Dental University, Department of Oral and Maxillofacial Surgery Kobe City General Hospital, Department of Oral and Maxillofacial Surgery Kobe City General Hospital, Second Department of Oral and Maxillofacial Surgery Osak Dental University, Second Department of Oral and Maxillofacial Surgery Osak Dental University

    Journal of Hard Tissue Biology   9巻2号41-46頁 ( 2 )   41 - 46   2000年

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    記述言語:英語   出版者・発行元:Society for Hard Tissue Regenerative Biology  

    The authors examined expression of keratin 19 by immunohistochemistry, reverse transcription-polymerase chain reaction(RT-PCR)and Northern blot analysis in benign ameloblastomas(n=10)and malignant ameloblastoma(n=1). Immunohistochemical expression of keratin was confined to the basal cells in normal gingival epithelia. in the stellate cells and squamous metaplastic cells in central nests of follicular ameloblastomas, and in peripheral cells of plexiform ameloblastomas. RT-PCR and Northern blot analysis showed that keratin 19 mRNA expression was sparse in the in gingiva, weak in plexiform ameloblastoma, moderate in follicular ameloblastoma, and intense in malignant ameloblastoma. In this study, we conclude that ameloblastoma cells that retain the characteristics of tooth germ may proliferate. The differentiation made of ameloblastoma and malignant ameloblastoma may be different from the stratification of squamous cell. Keratin 19 may not be useful as a malignant marker in ameloblastoma.

    CiNii Article

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    その他リンク: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=357284

  • 頬粘膜に発生した平滑筋腫の1例

    稲葉 裕明, 仁木 寛, 後藤 基宏, 内田 斉, 覚道 健治, 和唐 雅博

    日本口腔外科学会雑誌   45巻8号512-514頁 ( 8 )   512 - 514   1999年

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    記述言語:日本語   出版者・発行元:Japanese Society of Oral and Maxillofacial Surgeons  

    Leiomyoma is a benign tumor arising in smooth muscle. It occurs mainly in the uterus and stomach. However, it rarely occurs in the oral cavity. The patient had noticed swelling of the left side of the buccal mucosa about 7 years previously, but had ignored it. Because the tumor gradually grew larger, he came to our hospital in May 1997. Under the clinical diagnosis of a benign tumor of the left side of the buccal mucosa, we performed enucleation of the tumor under general anesthesia. The histopathlogical diagnosis was vascular leiomyoma. There has been no evidence of recurrence as of 11 months after surgery.

    DOI: 10.5794/jjoms.45.512

    CiNii Article

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    その他リンク: http://search.jamas.or.jp/link/ui/2000031379

▼全件表示

共同研究・競争的資金等の研究

  • 口腔バイオフィルム感染症制御法確立のための新規ターゲットタンパクの解析

    研究課題/領域番号:23H03115  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    仲野 道代, 仲 周平, 稲葉 裕明

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    配分額:18460000円 ( 直接経費:14200000円 、 間接経費:4260000円 )

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  • 膜タンパクをターゲットとした新たな口腔バイオフィルム制御法の確立

    研究課題/領域番号:20H03897  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    仲野 道代, 仲 周平, 稲葉 裕明

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    配分額:17290000円 ( 直接経費:13300000円 、 間接経費:3990000円 )

    バイオフィルム形成は、細胞―細胞間情報伝達機構であるクオラムセンシングにより制御されており、必要な栄養素を取り込み不要な物質を排出する役割を持つ膜タンパクが関与しているがその詳細は不明である。本研究では、分子生物学的手法を駆使して齲蝕および歯周病の主要な起炎菌における膜タンパクの役割を明らかにすることを目的としている。
    S. mutans UA159 株のデータベースから、バイオフィルム形成に関連すると推定されるABC 膜輸送体をコードするSMU _1519 遺伝子を抽出した。SMU _1519の上流および下流領域、およびスペクチノマイシン耐性カセット断片をPCRにて増幅した。オーバーラップPCRで3つのDNA断片を連結させ、精製した。PCR産物をMT8148 株に形質転換することによりSMU _1519欠失変異株(Δ1519株)を作製し、実験に供試した。これらの菌株を対数増殖期まで培養し,RNA抽出を行い,RNA シーケンシングを行った。親株と比較して,遺伝子欠失変異株で2倍以上の変化を認めた遺伝子の解析を行った。その結果、MT8148株と比較し,SMU_1519 遺伝子欠失株において2倍以上発現が抑制した遺伝子は,ガラクトースやラクトースの代謝に関与するlac遺伝子を含む46種類であった。2倍以上発現が上昇した遺伝子は,アンモニアのトランスポーターであるnrgAを含む56種類であった。また,CSP添加によってSMU_1519 遺伝子の発現に変化は認めなかった。以上の結果から、SMU_1519 遺伝子欠失によって糖代謝に重要な役割を果たすlacオペロンの発現が抑制されることから,SMU_1519 遺伝子は増殖能やバイオフィルム形成に関与するシグナル伝達系によって制御されていることが示唆された。

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  • 歯周病菌P. gulaeが保有する病原因子の分子生物学的解析とその多様性の解明

    研究課題/領域番号:20K09918  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    稲葉 裕明

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究費では動物由来歯周病菌Porphyromonas gulae のヒト歯肉上皮細胞への病原因子の影響を解析し、本菌による歯周病発症を詳細に理解することと、その制御法の開拓につながる知見を得ることを目的としている。
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    P. gulae の病原因子は、現在、線毛、タンパク分解酵素(プロテアーゼ)、LPSの存在が明らかにされているが、本研究課題でそれら病原因子の役割を解明する。昨年度研究までに、プロテアーゼは歯肉上皮細胞に存在する細胞接着、接着斑、フィブリノーゲン、フィブロネクチン、さらにはグロブリンを分解することを解明した。LPS解析では、LPSが歯肉上皮細胞の炎症反応を惹起することを明らかにした。線毛研究では、線毛欠損変異株の作製を進めた。
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    本年度研究内容を以下に示す。線毛解析:線毛欠損株ならびに同欠損株の相補株を完成させると共に、線毛欠損株と相補株の菌性状を確認した。線毛の有無以外、P. gulae 増殖能、黒色色素産生能に影響をおよぼさなかった。LPS解析:LPSに刺激された歯肉上皮細胞のToll様受容体2と4の活性を始めとする炎症反応までに至るシグナル伝達経路を、Toll様受容体ノックダウン細胞を用いて明らかにした。プロテアーゼ解析:プロテアーゼはP. gulaeが保有する血色素凝集能、菌増殖能ならびに口腔細菌 A. viscosusとの共凝集に影響をおよぼすことを明らかにした。また、歯肉上皮細胞の増殖能や細胞形態への変化に関与することも明らかにした。プロテアーゼに関連する遺伝子部位の塩基配列の決定が遅れているため、各種阻害剤を用い、触媒残基に基づく分類を進めている。

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  • 歯周病菌P. gulaeの歯肉上皮細胞への感染成立と歯周病発症メカニズムの解明

    研究課題/領域番号:17K11612  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    稲葉 裕明, 仲野 道代

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究費では、P. gulae 各線毛タイプ株のヒト歯肉上皮細胞株Ca9-22株への付着侵入をプロテクションアッセイを用いて解析した。全ての菌株が歯肉上皮細胞に付着するが、C型線毛保有の2株とB型線毛保有株1株のみ細胞内に侵入することが明らかにした。歯肉上皮細胞への付着侵入は、インテグリン&#593;5β1を介し、細胞膜のアクチン重合や代謝の調節因子だけでなく、菌が保有するプロテアーゼが関与することも明らかにした。C型線毛保有株の侵入能は、最も宿主傷害能を有するP. gingivalis II型線毛保有株と同等の侵入能を有することから、歯周病発症に関わる口腔細菌であることが示唆された。

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  • バイオフィルム感染症におけるABCトランスポーターの役割の探索と齲蝕予防への応用

    研究課題/領域番号:16H05550  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    仲野 道代, 高島 由紀子, 平野 慶子, 稲葉 裕明

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    配分額:16900000円 ( 直接経費:13000000円 、 間接経費:3900000円 )

    本研究では、グルタミンABCトランスポーター(GlnP) 欠失変異株(ΔGlnP)を作製し、バイオフィルムを形成させたところ、親株と比較して明らかに構造が変化していた。また、ΔGlnPでは膜流動性が変化し、耐酸性も著しく低下していた。さらに、シグナル伝達システムに関連する遺伝子のうちComCを欠失させた変異株では、GlnPおよび GlnPとオペロンを形成しているPIIプロテインの発現は顕著に低下していた。以上のことより、ABCトランスポーターは物資の膜輸送の機能を有しバイオフィルム形成におけるシグナル伝達システムに強く関与し、バイフォフィルム形成に重要な役割を果たしていることが明らかとなった。

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  • 歯周病原細菌による口腔癌の臓器転移に関する基礎的研究

    研究課題/領域番号:25462850  2013年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    稲葉 裕明, 野田 健司

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    Porphyromonas gingivalis に感染した口腔癌細胞株は、プロテアーゼ受容体2(PAR2)と4が活性化された。PAR2の活性化はNFkBを、PAR4の活性化はp38/HSP27とERK1/2-Ets1経路をそれぞれ活性化し、前駆体マトリックスメタロプロテアーゼ9(MMP9)の産生を亢進した。細胞外に分泌された前駆体MMP9は、P. gingivalisタンパク分解酵素により活性化され、口腔癌細胞の浸潤能を促進した。またP. gingivalis感染口腔扁平上皮癌細胞株の浸潤能促進は、アップル・ホップポリフェノールにより抑制された。

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  • オートファジーは歯周病菌が撹乱した細胞内秩序を再び律するのか?

    研究課題/領域番号:25293372  2013年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    野田 健司, 天野 敦雄, 稲葉 裕明

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    配分額:17420000円 ( 直接経費:13400000円 、 間接経費:4020000円 )

    歯周病は歯周病菌とよばれるPorphyromonus gingivalisをはじめとした細菌群の定着感染に惹起される歯肉および歯槽骨での上皮、マクロファージ、破骨細胞などの可能な免疫反応がその病因である。この発症過程においてエンドサイトーシスおよびオートファジーがどのように関与するのかはほぼ不明であった。本研究により、Porphyromonus gingivalisの感染にLYSTを介したエンドサイトーシス、および破骨細胞で特異的に発現するタンパク質を介したミクロオートファジーが発見され、それらが歯周病発症に関与する可能性が示唆された。

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  • 歯周病菌―サイトメガロウイルス重複感染モデルによる早産誘発機構の解析

    研究課題/領域番号:23792102  2011年 - 2012年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    稲葉 裕明

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    歯周病菌Porphyromonas gingivalisのヒト胎盤栄養膜細胞への感染は、ATR/Chk2/p53のDNA傷害シグナル伝達経路とERK1/2-Ets1の複数経路を介して、G1期細胞周期停止とアポトーシスが促進された。さらに、P. gingivalisの感染は、p53の活性化を抑制するMDM2がジンジパインにより特異的に分解されることにより、p53の蓄積が亢進し、G1期細胞周期停止およびアポトーシスが促進されることが明らかになった

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  • メンブレントラフィックから見た歯周病の早産誘発機構の分子基盤研究

    研究課題/領域番号:22659378  2010年 - 2011年

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    天野 敦雄, 稲葉 裕明, 古田 信道

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    配分額:3190000円 ( 直接経費:2800000円 、 間接経費:390000円 )

    歯周病は早産・低体重出生児の危険因子であると考えられており、動物実験により歯周病菌Porphyromonas gingivalisの血行性感染が原因の1つと考えられている。しかしながら、その発症機序は不明であった。我々はP. gingivalisに侵入されたトロホブラスト細胞では細胞周期G1アレストやDNA傷害が誘発されることを報告した。本研究では、本菌が細胞侵入後、細胞傷害性を発揮するシグナル経路を探索した結果、本菌のジンジパインが細胞周期G1アレストやアポトーシスを誘導することが示唆された。

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  • 動物実験モデルを用いた歯周病原菌の動脈硬化病変形成能の評価

    研究課題/領域番号:18791347  2006年 - 2007年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    稲葉 裕明

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    配分額:3400000円 ( 直接経費:3400000円 )

    現在、動脈血中に移行した歯周病菌Porphyromonas gingivalisがアテローム形成を促進する可能性が論じられている。しかし,Porphyromonas gingivalisと心臓血管疾患との因果関係は未だ解明されていない.そこで本年度は、閉塞性動脈硬化症患者の手術摘出組織試料および口腔内プラークから歯周病原性菌の検出を評価した。
    大阪労災病院心臓血管外科より56症例分供与された、閉塞性動脈硬化症患者の手術摘出組織試料および口腔内プラークより細菌DNAを抽出し、PCR法により歯周病原性菌(P.gingivalis, P.intermedia, A.actinomycetemcomitans, T.denticola, T.forsythia, C.rectus, Streptcoccus属)の検出を試みた。
    P.gingivalis, A.actinomycetemcomitans, T.denticola, P.intermediaが摘出組織より検出され、更に口腔内で検出されたP.gingivalis, A.actinomycetemcomitans, S.mutansと摘出組織中から検出された各菌の遺伝子型(線毛、血清型)を確認したところ、すべての症例で同じ遺伝子型が検出された。この結果は、口腔内細菌の血中への感染により動脈壁へ付着し、本疾患を誘発する可能性を示唆している。
    現在、光照射により大腿動脈の血管内皮を傷害したモデルマウスにこれらの菌株を感染させ、梗塞性病変形成との関連を評価中である。また同時に、感染させたモデルマウスの大腿動脈のマイクロアレイ解析を実施し、梗塞性疾患と歯周病感受性と関連する遺伝子を検索している。

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  • 細菌感染によるオートファジー誘導の分子機構の解明

    研究課題/領域番号:18050018  2006年 - 2007年

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    天野 敦雄, 中川 一路, 稲葉 裕明

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    配分額:6600000円 ( 直接経費:6600000円 )

    歯周病細菌の宿主細胞内侵入経路および、細胞内侵入後の同菌の細胞内動態につき検討を加えた。オートファジーが細胞内に侵入した細菌を駆逐する分子メカニズムについても検討を加えた。その結果、下記3つの知見が得られた。
    1.歯周病細菌P.gingivalisの細胞侵入に関与する宿主因子は、リピッドラフト、α5β1インテグリン、small-GTPaseのRacl、アクチン、微小管の他、アクチンの再構築やエシドサイトーシスに関わる分子であった。
    2.エンドサイトーシス経路を利用して細胞内に侵入した歯周病紬菌は、一部は後期エンドソームに包まれたまま分解されてしまうが、一部は初期エンドソームから脱出し、細胞質内に留まる菌と、オートファジーによって殺される菌とがあることが示された。このオートファジー誘導のメカニズムについては明確な結果が得られなかった。今後の研究課題である。
    3.歯周病細菌の細胞侵入に不可央な線毛には6つの遺伝子多型が存在し、II型線毛遺伝子をもつ菌株は効率よく歯周細胞に侵入し、強力な細胞機能傷害と細胞死を引き起こすことを示した。

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  • 歯肉上皮細胞によるP.gingivalis殺菌機構と歯周病感受性との関連の解析

    研究課題/領域番号:17390559  2005年 - 2007年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    天野 敦雄, 中川 一路, 稲葉 裕明, 河合 伸治

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    配分額:16210000円 ( 直接経費:15400000円 、 間接経費:810000円 )

    Porphyromonas gingivalisの宿主細胞内侵入経路および、細胞内侵入後の同菌の細胞内動態につき検討を加えた。その結果、下記3つの知見が得られた。
    1.P.gingivalisの細胞侵入に関与する宿主因子は、リピッドラフト、α5β1インテグリン、small-GTPaseのRac1、アクチン、微小管の他アクチンの再構築やエンドサイトーシスに関わる分子であることが示された。
    2.エンドサイトーシス経路を利用して細胞内に侵入したP.gingivalisは、一部は後期エンドソームに包まれたまま分解されてしまうが、一部は初期エンドソームから脱出し、細胞質内に留まる菌と、オートファジーによって殺される菌とがあることが示された。この違いが何故起こるのかは不明であり、今後の研究課題である。
    3.P.gingivalisの細胞侵入に不可欠な線毛には6つの遺伝子多型が存在し、II型線毛遺伝子をもつ菌株は効率よく歯周細胞に侵入し、強力な細胞機能傷害と細胞死を引き起こすことを示した。
    今後さらに歯周感染から宿主を防御するメンブレントラフィックの自然免疫機能の分子基盤を明らかにするとともに、侵入してきた歯周病菌を細胞が殺すためのメンブレントラフィック機能の個人差と歯周病感受性との関連に検討を加える。

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社会貢献活動

  • Oral Health Management for Children, Adolescents, and Adults, 2nd Volume

    役割:編集

    MDPI  Topic Editor  2023年4月 - 現在

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  • Journal of Oral Microbiology

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    Editorial Board  2023年3月 - 現在

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  • Frontiers in Immunology

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    Associate Editor  2022年5月 - 現在

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  • Oral Health Management for Children, Adolescents, and Adults

    役割:編集

    MDPI  Topic Editor  2021年1月

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学術貢献活動

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    2023年1月

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    2022年7月

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  • International Journal of Environmental Research and Public Health

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    2022年4月25日

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    2021年11月

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    2021年5月

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