Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Associate Professor
Position
Associate Professor
External link
NAKAYAMA Masaaki
Degree
Degree
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PhD ( 2006.3 Nagasaki University )
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Master (Engineering) ( 2002.3 Nagasaki University )
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Bachelor (Engineering) ( 2000.3 Nagasaki University )
Research Areas
Research Areas
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Life Science / Oral pathobiological science
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Life Science / Bacteriology
Education
Education
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Nagasaki University 工学部 応用化学科
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Nagasaki University 大学院医歯薬学総合研究科 新興感染症病態制御学系専攻
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Nagasaki University 大学院生産科学研究科 物質工学専攻
Research History
Research History
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Okayama University 学術研究院医歯薬学域 Associate Professor
2023.1
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Okayama University 学術研究院医歯薬学域 Assistant Professor
2021.4 - 2022.12
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Okayama University 大学院医歯薬学総合研究科 Assistant Professor
2010.3 - 2021.3
Professional Memberships
Professional Memberships
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岡山歯学会
2023.1
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抗酸菌研究会
2018.4
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口腔微生物学・微生物研究会
2013.4
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歯科基礎医学会
2012.7
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日本細菌学会
2010.3
Papers
Papers
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Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma. International journal
Htoo Shwe Eain, Hotaka Kawai, Masaaki Nakayama, May Wathone Oo, Toshiaki Ohara, Yoko Fukuhara, Kiyofumi Takabatake, Quisheng Shan, Yamin Soe, Kisho Ono, Keisuke Nakano, Nobuyoshi Mizukawa, Seiji Iida, Hitoshi Nagatsuka
JCI insight 9 ( 10 ) 2024.5
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Language：English Publishing type：Research paper (scientific journal)
Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro-tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph-circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.
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Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans. International journal
Yuki Shinoda-Ito, Kazuhiro Omori, Takashi Ito, Masaaki Nakayama, Atsushi Ikeda, Masahiro Ito, Toshiaki Ohara, Shogo Takashiba
Antibiotics (Basel, Switzerland) 12 ( 11 ) 2023.10
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Language：English Publishing type：Research paper (scientific journal)
Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.
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Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans. International journal
Yuki Shinoda-Ito, Kazuhiro Omori, Takashi Ito, Masaaki Nakayama, Atsushi Ikeda, Masahiro Ito, Toshiaki Ohara, Shogo Takashiba
Antibiotics (Basel, Switzerland) 12 ( 11 ) 2023.10
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Language：English Publishing type：Research paper (scientific journal)
Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.
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Association of illness perception and alexithymia with fatigue in hemodialysis recipients: a single-center, cross-sectional study. International journal
Yoko Tanemoto, Ui Yamada, Masaaki Nakayama, Takeaki Takeuchi, Fumiaki Tanemoto, Yugo Ito, Daiki Kobayashi, Daisuke Ohta, Masahiro Hashizume
Scientific reports 13 ( 1 ) 16592 - 16592 2023.10
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Language：English Publishing type：Research paper (scientific journal)
Fatigue in hemodialysis recipients interferes with daily activities and renal rehabilitation, and its underlying causes and treatment remain unclear. Psychological factors, like illness perceptions and alexithymia, cause fatigue in other diseases; however, their contribution to hemodialysis-related fatigue is unknown. This cross-sectional study included 53 hemodialysis recipients. To assess participants' fatigue, we used a self-administered patient-reported outcome questionnaire whose items have shown correlation with those of established scales, such as the Profile of Mood States and Visual Analogue Scales. The associations among the scores of the revised Illness Perceptions Questionnaire (IPQ-R), Toronto Alexithymia Scale (TAS-20), and Hospital Anxiety and Depression Scale and fatigue were analyzed using bivariable and multivariable analyses. Patients with fatigue had significantly higher median scores for the IPQ-R subscales "Identity" and "Negative emotional representation about illness" than those without fatigue, suggesting the association of specific illness perception with fatigue. Median scores for the TAS-20 subscale "Difficulty identifying feelings" were also significantly higher among fatigued patients, suggesting the association of alexithymia with fatigue. Depression was not associated with fatigue. Multivariable logistic regression revealed the association of a high "Identity" score with the risk of fatigue (adjusted odds ratio, 1.32; 95% confidence interval, 1.00-1.73; P = 0.04), while there were no significant association between a high "Difficulty identifying feelings" score and the risk of fatigue (adjusted odds ratio, 1.09; 95% confidence interval, 0.95-1.24). Specific illness perception and alexithymia were slightly associated with hemodialysis-related fatigue. Cognitive-behavioral therapy for these conditions could reduce fatigue and promote renal rehabilitation.
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Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.
Masaaki Nakayama, Masanobu Miyazaki, Chieko Hamada, Yasuhiko Ito, Kazuho Honda
Clinical and experimental nephrology 27 ( 9 ) 717 - 727 2023.9
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Language：English Publishing type：Research paper (scientific journal)
Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.
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口腔癌におけるCX3CL1とリンパ節転移の関係(Relationship between CX3CL1 and lymph node metastasis in oral cancer)
河合 穂高, トゥ・シュエイン, 中山 真彰, 大原 利章, 長塚 仁
日本癌学会総会記事 82回 1421 - 1421 2023.9
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口腔癌におけるCX3CL1とリンパ節転移の関係(Relationship between CX3CL1 and lymph node metastasis in oral cancer)
河合 穂高, トゥ・シュエイン, 中山 真彰, 大原 利章, 長塚 仁
日本癌学会総会記事 82回 1421 - 1421 2023.9
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Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba
Journal of Fungi 9 ( 3 ) 314 - 314 2023.3
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Publishing type：Research paper (scientific journal) Publisher：MDPI AG
Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.
DOI： 10.3390/jof9030314
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The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model. International journal
Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba
Journal of fungi (Basel, Switzerland) 9 ( 3 ) 2023.3
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Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.
DOI： 10.3390/jof9030314
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侵襲性歯周炎の血液診断マーカー候補となる細胞外小胞由来マイクロRNAとその炎症誘導機構の探索
森 彩乃, 山本 直史, 井手口 英隆, 河村 麻理, 河本 美奈, 伊東 昌洋, 小野 喜章, 中山 真彰, 江口 傑徳, 大野 充昭, 大森 一弘, 高柴 正悟
日本歯周病学会会誌 64 ( 春季特別 ) 114 - 114 2022.5
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Porphyromonas gingivalis Gingipains Induce Cyclooxygenase-2 Expression and Prostaglandin E2 Production via ERK1/2-Activated AP-1 (c-Jun/c-Fos) and IKK/NF-κB p65 Cascades. Reviewed International journal
Masaaki Nakayama, Mariko Naito, Kazuhiro Omori, Shintaro Ono, Koji Nakayama, Naoya Ohara
Journal of immunology (Baltimore, Md. : 1950) 208 ( 5 ) 1146 - 1154 2022.3
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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Porphyromonas gingivalis is commonly known as one of the major pathogens contributing to periodontitis, and its persistent infection may increase the risk for the disease. The proinflammatory mediators, including IL-6, TNF-α, and cyclooxygenase-2 (COX-2)/PGE2, are closely associated with progression of periodontitis. In this study, we focused on the cysteine protease "gingipains," lysine-specific gingipain, arginine-specific gingipain (Rgp) A, and RgpB, produced by P. gingivalis, and used the wild-type strain and several gene-deletion mutants (rgpA, rgpB, kgp, and fimA) to elucidate the involvement of gingipains in COX-2 expression and PGE2 production. We infected human monocytes, which are THP-1 cells and primary monocytes, with these bacterial strains and found that gingipains were involved in induction of COX-2 expression and PGE2 production. We have shown that the protease activity of gingipains was crucial for these events by using gingipain inhibitors. Furthermore, activation of ERK1/2 and IκB kinase was required for gingipain-induced COX-2 expression/PGE2 production, and these kinases activated two transcription factors, c-Jun/c-Fos (AP-1) and NF-κB p65, respectively. In particular, these data suggest that gingipain-induced c-Fos expression via ERK is essential for AP-1 formation with c-Jun, and activation of AP-1 and NF-κB p65 plays a central role in COX-2 expression/PGE2 production. Thus, we show the (to our knowledge) novel finding that gingipains with the protease activity from P. gingivalis induce COX-2 expression and PGE2 production via activation of MEK/ERK/AP-1 and IκB kinase/NF-κB p65 in human monocytes. Hence it is likely that gingipains closely contribute to the inflammation of periodontal tissues.
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Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG Reviewed
Yuki Arimura, Yusuke Minato, Takayuki Wada, Masaaki Nakayama, Ayako Ryumon, Nao Hirata, Chie Nakajima, Yasuhiko Suzuki, Manabu Ato, Kazuo Kobayashi, Naoko Ohara, Seiji Iida, Naoya Ohara
Microbiology and Immunology 66 ( 1 ) 10 - 14 2022.1
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Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley
Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1348-0421.12944
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Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG. International journal
Yuki Arimura, Yusuke Minato, Takayuki Wada, Masaaki Nakayama, Ayako Ryumon, Nao Hirata, Chie Nakajima, Yasuhiko Suzuki, Manabu Ato, Kazuo Kobayashi, Naoko Ohara, Seiji Iida, Naoya Ohara
Microbiology and immunology 66 ( 1 ) 10 - 14 2022.1
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Mycobacterium tuberculosis, the causative agent of tuberculosis, possess flavin-dependent thymidylate synthase, ThyX. Since thyX is absent in humans and was shown to be essential for M. tuberculosis normal growth, ThyX is thought to be an attractive novel TB drug target. This study assessed thyX essentiality in Mycobacterium bovis BCG strains using CRISPR interference based gene silencing and found that thyX is not essential in an M. bovis BCG Tokyo derivative strain. A thyX deletion mutant strain was successfully constructed from that strain, which reinforces the non-essentiality of thyX under a certain genetic background.
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GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation. International journal
Tomomi Kurane, Tetsuro Matsunaga, Tomoaki Ida, Kazuko Sawada, Akira Nishimura, Masayuki Fukui, Masayuki Umemura, Masaaki Nakayama, Naoya Ohara, Sohkichi Matsumoto, Takaaki Akaike, Goro Matsuzaki, Giichi Takaesu
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 ( 1 ) e22096 2022.1
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Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn2+ metalloprotease 1 (Zmp1) is known to suppress interleukin (IL)-1β production by inhibiting caspase-1 resulting in phagosome maturation arrest. However, the molecular mechanism of caspase-1 inhibition by Zmp1 is still elusive. Here, we identified GRIM-19 (also known as NDUFA13), an essential subunit of mitochondrial respiratory chain complex I, as a novel Zmp1-binding protein. Using the CRISPR/Cas9 system, we generated GRIM-19 knockout murine macrophage cell line J774.1 and found that GRIM-19 is essential for IL-1β production during mycobacterial infection as well as in response to NLRP3 inflammasome-activating stimuli such as extracellular ATP or nigericin. We also found that GRIM-19 is required for the generation of mitochondrial reactive oxygen species and NLRP3-dependent activation of caspase-1. Loss of GRIM-19 or forced expression of Zmp1 resulted in a decrease in mitochondrial membrane potential. Our study revealed a previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1β production during mycobacterial infection.
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GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation Reviewed
Tomomi Kurane, Tetsuro Matsunaga, Tomoaki Ida, Kazuko Sawada, Akira Nishimura, Masayuki Fukui, Masayuki Umemura, Masaaki Nakayama, Naoya Ohara, Sohkichi Matsumoto, Takaaki Akaike, Goro Matsuzaki, Giichi Takaesu
The FASEB Journal 2021.12
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フッ化ナトリウムによるCCNファミリー遺伝子制御を介した歯肉線維化抑制作用の検討
水川 朋美, 西田 崇, 明石 翔, 大杉 綾花, 大森 一弘, 中山 真彰, 高柴 正悟, 上岡 寛, 滝川 正春, 久保田 聡
岡山歯学会雑誌 40 ( 2 ) 34 - 35 2021.12
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Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG. Reviewed
Yuki Arimura, Yusuke Minato, Takayuki Wada, Masaaki Nakayama, Ayako Ryumon, Nao Hirata, Chie Nakajima, Yasuhiko Suzuki, Manabu Ato, Kazuo Kobayashi, Naoko Ohara, Seiji Iida, Naoya Ohara
Microbiol Immunol. 2021.9
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Language：English Publishing type：Research paper (scientific journal)
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The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation. Reviewed International journal
Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba
Frontiers in pharmacology 12 674366 - 674366 2021.6
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Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.
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Tomomi Kawakita, Tetsu Mukai, Mitsunori Yoshida, Hiroyuki Yamada, Masaaki Nakayama, Yuji Miyamoto, Masato Suzuki, Noboru Nakata, Takemasa Takii, Akihide Ryo, Naoya Ohara, Manabu Ato
Microbiology 167 ( 2 ) 2021.2
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Language：English Publishing type：Research paper (scientific journal) Publisher：Microbiology Society
Mycobacterium avium subspecies hominissuis (MAH) is a pathogen that causes various non-tuberculous mycobacterial diseases in humans and animals worldwide. Among the genus, MAH is characterized by relatively slow growth. Here, we isolated a rapidly growing variant of the MAH 104 strain. The variant strain (named N104) exhibited an enhanced growth rate and higher motility compared to the parent MAH 104 strain (P104). Whole-genome sequencing analysis of N104 revealed the loss of the stop codon of MAV_RS14660 due to a single nucleotide replacement, resulting in the substitution of the codon for tryptophan. Notably, exclusion of the stop codon ligated the open reading frames and caused the fusion of two adjacent proteins. A revertant parent strain, in which a mutation was introduced to restore the stop codon, revealed that elimination of the stop codon in MAV_RS14660 was responsible for the N104 phenotype. Furthermore, we analysed the phenotypes of the parent and mutated strains by determining the functions of the MAV_RS14660 and MAV_RS14655 coding regions flanking the stop codon. The mutant strains, expected to express a fusion protein, exhibited increased resistance to antimicrobial drugs and exogenous copper toxicity compared to that of the parent strains. These findings suggest that the fusion of the MAV_RS14660- and MAV_RS14655-encoding regions in the mutant N104 strain could be related to the modified functions of these intrinsic proteins.
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Point mutation in the stop codon of MAV_RS14660 increases the growth rate of Mycobacterium avium subspecies hominissuis. International journal
Tomomi Kawakita, Tetsu Mukai, Mitsunori Yoshida, Hiroyuki Yamada, Masaaki Nakayama, Yuji Miyamoto, Masato Suzuki, Noboru Nakata, Takemasa Takii, Akihide Ryo, Naoya Ohara, Manabu Ato
Microbiology (Reading, England) 167 ( 2 ) 2021.2
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Language：English Publishing type：Research paper (scientific journal)
Mycobacterium avium subspecies hominissuis (MAH) is a pathogen that causes various non-tuberculous mycobacterial diseases in humans and animals worldwide. Among the genus, MAH is characterized by relatively slow growth. Here, we isolated a rapidly growing variant of the MAH 104 strain. The variant strain (named N104) exhibited an enhanced growth rate and higher motility compared to the parent MAH 104 strain (P104). Whole-genome sequencing analysis of N104 revealed the loss of the stop codon of MAV_RS14660 due to a single nucleotide replacement, resulting in the substitution of the codon for tryptophan. Notably, exclusion of the stop codon ligated the open reading frames and caused the fusion of two adjacent proteins. A revertant parent strain, in which a mutation was introduced to restore the stop codon, revealed that elimination of the stop codon in MAV_RS14660 was responsible for the N104 phenotype. Furthermore, we analysed the phenotypes of the parent and mutated strains by determining the functions of the MAV_RS14660 and MAV_RS14655 coding regions flanking the stop codon. The mutant strains, expected to express a fusion protein, exhibited increased resistance to antimicrobial drugs and exogenous copper toxicity compared to that of the parent strains. These findings suggest that the fusion of the MAV_RS14660- and MAV_RS14655-encoding regions in the mutant N104 strain could be related to the modified functions of these intrinsic proteins.
DOI： 10.1099/mic.0.001007
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Construction and Characterization of the PGN_0296 Mutant of Porphyromonas gingivalis Reviewed
Abu Saleh Muhammad Shahriar, Shintaro Ono, Masaaki Nakayama, Naoko Ohara and Naoya Ohara
Journal of Oral Biosciences 2020.10
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The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1 Reviewed
Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba
International Immunopharmacology 83 2020.6
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Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.
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The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. International journal
Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba
International immunopharmacology 83 106429 - 106429 2020.6
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Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.
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PCRをベースとしたLautropia mirabilisの簡便な検出法と分離法の検討
佐藤 あやめ, 中山 真彰, 中川 美緒, 小崎 弘貴, 室 美里, 曽我 賢彦, 大原 直也
日本細菌学雑誌 75 ( 1 ) 66 - 66 2020.1
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Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: evidence for contribution of PGN_0297 to gingipain activity Reviewed
Shintaro Ono, Masaaki Nakayama, Masato Tachibana, Abu Saleh Muhammad Shahriar, Wang Heling, Shogo Takashiba, and Naoya Ohara
Acta Medica Okayama 2019.3
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Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: Evidence of the contribution of PGN_0297 to gingipain activity
Shintaro Ono, Masaaki Nakayama, Masato Tachibana, Abu Saleh Muhammad Shahriar, Wang Heling, Shogo Takashiba, Naoya Ohara
Acta Medica Okayama 73 ( 4 ) 315 - 323 2019
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Language：English Publishing type：Research paper (scientific journal) Publisher：Okayama University
The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism's virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains.
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Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts. Reviewed International journal
Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba
Heliyon 4 ( 11 ) e00979 2018.11
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Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.
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Fungal metabolite (
Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba
HELIYON 4 ( 11 ) 2018.11
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Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD
Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.
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Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway Invited Reviewed
Nakayama Masaaki, Ohara Naoya
JOURNAL OF ORAL BIOSCIENCES 59 ( 3 ) 131 - 134 2017.8
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Language：English Publisher：Japanese Association for Oral Biology
Background Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection. Highlight Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation. Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades. Conclusion This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.
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Involvement of an Skp-Like Protein, PGN_0300, in the Type IX Secretion System of Porphyromonas gingivalis Reviewed
Yuko Taguchi, Keiko Sato, Hideharu Yukitake, Tetsuyoshi Inoue, Masaaki Nakayama, Mariko Naito, Yoshio Kondo, Konami Kano, Tomonori Hoshino, Koji Nakayama, Shogo Takashiba, Naoya Ohara
INFECTION AND IMMUNITY 84 ( 1 ) 230 - 240 2016.1
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Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC MICROBIOLOGY
The oral Gram-negative anaerobic bacterium Porphyromonas gingivalis is an important pathogen involved in chronic periodontitis. Among its virulence factors, the major extracellular proteinases, Arg-gingipain and Lys-gingipain, are of interest given their abilities to degrade host proteins and process other virulence factors. Gingipains possess C-terminal domains (CTDs) and are translocated to the cell surface or into the extracellular milieu by the type IX secretion system (T9SS). Gingipains contribute to the colonial pigmentation of the bacterium on blood agar. In this study, Omp17, the PGN_0300 gene product, was found in the outer membrane fraction. A mutant lacking Omp17 did not show pigmentation on blood agar and showed reduced proteolytic activity of the gingipains. CTD-containing proteins were released from bacterial cells without cleavage of the CTDs in the omp17 mutant. Although synthesis of the anionic polysaccharide (A-LPS) was not affected in the omp17 mutant, the processing of and A-LPS modification of CTD-containing proteins was defective. PorU, a C-terminal signal peptidase that cleaves the CTDs of other CTD-containing proteins, was not detected in any membrane fraction of the omp17 mutant, suggesting that the defective maturation of CTD-containing proteins by impairment of Omp17 is partly due to loss of function of PorU. In the mouse subcutaneous infection experiment, the omp17 mutant was less virulent than the wild type. These results suggested that Omp17 is involved in P. gingivalis virulence.
DOI： 10.1128/IAI.01308-15
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BCG thyX欠損株の作製とその性状解析
有村 友紀, 中山 真彰, 妹尾 昌紀, 田川 淳平, 中山 浩次, 飯田 征二, 大原 直也
Journal of Oral Biosciences Supplement 2015 330 - 330 2015.9
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BCGにおけるcyclic-di-GMP菌体内合成の影響
妹尾 昌紀, 中山 真彰, 有村 友紀, 飯田 征二, 大原 直也
Journal of Oral Biosciences Supplement 2015 331 - 331 2015.9
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Involvement of an Skp-like protein, PGN_0300, in the type IX secretion system of Porphyromonas gingivalis Reviewed
Yuko Taguchi , Keiko Sato , Hideharu Yukitake , Tetsuyoshi Inoue , Masaaki Nakayama , Mariko Naito , Yoshio Kondo , Konami Kano , Tomonori Hoshino , Koji Nakayama , Shogo Takashiba and Naoya Ohara
Infection and Immunity 290 ( 8 ) 5190 - 5202 2015.2
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Attenuation of the phosphatidylinositol 3-Kinase/Akt signaling pathway by porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp
Masaaki Nakayama, Tetsuyoshi Inoue, Mariko Naito, Koji Nakayama, Naoya Ohara
Journal of Biological Chemistry 290 ( 8 ) 5190 - 5202 2015.2
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Language：English Publishing type：Research paper (scientific journal) Publisher：American Society for Biochemistry and Molecular Biology Inc.
Background: The significance of gingipains on the PI3K/Akt signaling pathway is poorly understood.Results: The inactivation of PI3K and Akt was induced by P. gingivalis, which was associated with gingipains.Conclusion: Gingipains are critical for suppressing the PI3K/Akt signaling pathway via extracellular proteolysis independent of P. gingivalis invasion. Significance: This study shows the first evidence that the gingipains negatively regulate the PI3K/Akt signaling pathway.
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Attenuation of the PI3 kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp Reviewed
Masaaki Nakayama, Tetsuyoshi Inoue, Mariko Naito, Koji Nakayama and Naoya Ohara
The Journal of Biological Chemistry 290 ( 8 ) 5190 - 5202 2015.1
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Characterization of the tripartite drug efflux pumps of Porphyromonas gingivalis ATCC 33277 Reviewed
Tetsuyoshi Inoue, Masaaki Nakayama, Yuko Taguchi, Konami Kano, Miyuu Ono, Yurika Shimizu, Teruo Kuroda, Naoya Ohara
New Microbiologica 38 ( 1 ) 97 - 103 2015.1
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Role of extracytoplasmic function sigma factors in biofilm formation of Porphyromonas gingivalis. Reviewed International journal
Satosu Onozawa, Yuichiro Kikuchi, Kazuko Shibayama, Eitoyo Kokubu, Masaaki Nakayama, Tetsuyoshi Inoue, Keisuke Nakano, Yukinaga Shibata, Naoya Ohara, Koji Nakayama, Kazuyuki Ishihara, Toshiyuki Kawakami, Hiromasa Hasegawa
BMC oral health 15 4 - 4 2015.1
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BACKGROUND: Porphyromonas gingivalis has been implicated as a major pathogen in the development and progression of chronic periodontitis. P. gingivalis biofilm formation in the subgingival crevice plays an important role in the ability of the bacteria to tolerate stress signals outside the cytoplasmic membrane. Some bacteria use a distinct subfamily of sigma factors to regulate their extracytoplasmic functions (the ECF subfamily). The objective of this study was to determine if P. gingivalis ECF sigma factors affect P. gingivalis biofilm formation. METHODS: To elucidate the role of ECF sigma factors in P. gingivalis, chromosomal mutants carrying a disruption of each ECF sigma factor-encoding gene were constructed. Bacterial growth curves were measured by determining the turbidity of bacterial cultures. The quantity of biofilm growing on plates was evaluated by crystal violet staining. RESULTS: Comparison of the growth curves of wild-type P. gingivalis strain 33277 and the ECF mutants indicated that the growth rate of the mutants was slightly lower than that of the wild-type strain. The PGN_0274- and PGN_1740-defective mutants had increased biofilm formation compared with the wild-type (p < 0.001); however, the other ECF sigma factor mutants or the complemented strains did not enhance biofilm formation. CONCLUSION: These results suggest that PGN_0274 and PGN_1740 play a key role in biofilm formation by P. gingivalis.
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Development of a novel plasmid vector pTIO-1 adapted for electrotransformation of Porphyromonas gingivalis Reviewed
Junpei Tagawa, Tetsuyoshi Inoue, Mariko Naito, Keiko Sato, Tomomi Kuwahara, Masaaki Nakayama, Koji Nakayama, Takashi Yamashiro, Naoya Ohara
JOURNAL OF MICROBIOLOGICAL METHODS 105 174 - 179 2014.10
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Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV
We report here the construction of a plasmid vector designed for the efficient electrotransformation of the periodontal pathogen Porphyromonas gingivalis. The novel Escherichia coli-Bacteroides/P. gingivalis shuttle vector, designated pTIO-1, is based on the 11.0-kb E. coli-Bacteroides conjugative shuttle vector, pVAL-1 (a pB8-51 derivative). To construct pTIO-1, the pB8-51 origin of replication and erythromycin resistance determinant of pVAL-1 were cloned into the E. coli cloning vector pBluescript II SK(-) and non-functional regions were deleted. pTIO-1 has an almost complete multiple cloning site from pBluescript II SK(-). The size of pTIO-1 is 4.5 kb, which is convenient for routine gene manipulation. pTIO-1 was introduced into P. gingivalis via electroporation, and erythromycin-resistant transformants carrying pTIO-1 were obtained. We characterized the transformation efficiency, copy number, host range, stability, and insert size capacity of pTIO-1. An efficient plasmid electrotransformation of P. gingivalis will facilitate functional analysis and expression of P. gingivalis genes, including the virulence factors of this bacterium. (C) 2014 Elsevier B.V. All rights reserved.
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Development of a novel plasmid vector pTIO-1 adapted for electrotransformation of Porphyromonas gingivalis Reviewed
Junpei Tagawa, Tetsuyoshi Inoue, Mariko Naito, Keiko Sato, Tomomi Kuwahara, Masaaki Nakayama, Koji Nakayama, Takashi Yamashiro, Naoya Ohara
Journal of Microbiological Methods 2014.8
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Yuki Fujita, Masaaki Nakayama, Mariko Naito, Eiki Yamachika, Tetsuyoshi Inoue, Koji Nakayama, Seiji Iida, Naoya Ohara
Infection and Immunity 82 ( 1 ) 202 - 211 2014.1
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Language：English Publishing type：Research paper (scientific journal) Publisher：American Society for Microbiology
ABSTRACT
Periodontitis is an inflammatory disease of polymicrobial origin affecting the tissues supporting the tooth. The oral anaerobic bacterium Porphyromonas gingivalis , which is implicated as an important pathogen for chronic periodontitis, triggers a series of host inflammatory responses that promote the destruction of periodontal tissues. Among the virulence factors of P. gingivalis , hemoglobin receptor protein (HbR) is a major protein found in culture supernatants. In this study, we investigated the roles of HbR in the production of inflammatory mediators. We found that HbR induced interleukin-8 (IL-8) production in the human gingival epithelial cell line Ca9-22. p38 mitogen-activated protein kinase (MAPK) and extracellular signal-related kinase 1/2 (Erk1/2) were activated in HbR-stimulated Ca9-22 cells. Inhibitors of p38 MAPK (SB203580) and Erk1/2 (PD98059) blocked HbR-induced IL-8 production. Additionally, HbR stimulated the translocation of NF-κB-p65 to the nucleus, consistent with enhancement of IL-8 expression by activation of the NF-κB pathway. In addition, small interfering RNA (siRNA) targeting activating transcription factor 2 (ATF-2) or cyclic AMP-response element-binding protein (CREB) inhibited HbR-induced IL-8 production. Moreover, pretreatment with SB203580 and PD98059 reduced HbR-induced phosphorylation of CREB and ATF-2, respectively. Combined pretreatment with an inhibitor of NF-κB (BAY11-7082) and SB203580 was more efficient in inhibiting the ability of HbR to induce IL-8 production than pretreatment with either BAY11-7082 or SB203580 alone. Thus, in Ca9-22 cells, the direct activation of p38 MAPK and Erk1/2 by HbR caused the activation of the transcription factors ATF-2, CREB, and NF-κB, thus resulting in the induction of IL-8 production.DOI： 10.1128/iai.01140-12
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Porphyromonas gingivalisにおいて電気穿孔法で導入可能なプラスミドベクターの構築
田川 淳平, 井上 哲圭, 佐藤 啓子, 内藤 真理子, 中山 真彰, 中山 浩次, 山城 隆, 大原 直也
Journal of Oral Biosciences Supplement 2013 113 - 113 2013.9
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Porphyromonas gingivalisにおいて電気穿孔法で導入可能なプラスミドベクターの構築
田川 淳平, 井上 哲圭, 佐藤 啓子, 内藤 真理子, 中山 真彰, 中山 浩次, 山城 隆, 大原 直也
Journal of Oral Biosciences Supplement 2013 167 - 167 2013.9
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Interweaving MicroRNAs and Proinflammatory Cytokines in Gastric Mucosa with Reference to H. pylori Infection (共著) Reviewed
Journal of Clinical Immunology 2012.4
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Interweaving MicroRNAs and Proinflammatory Cytokines in Gastric Mucosa with Reference to H. pylori Infection Reviewed
Hajime Isomoto, Kayoko Matsushima, Naoki Inoue, Tomayoshi Hayashi, Toshiyuki Nakayama, Masaki Kunizaki, Shigekazu Hidaka, Masaaki Nakayama, Junzo Hisatsune, Masahiro Nakashima, Takeshi Nagayasu, Kazuhiko Nakao, Toshiya Hirayama
JOURNAL OF CLINICAL IMMUNOLOGY 32 ( 2 ) 290 - 299 2012.4
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Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER/PLENUM PUBLISHERS
Using endoscopic biopsies, gastric mucosal expression levels of interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) and microRNAs (miRNAs) that were differentially expressed in association with Helicobacter pylori were assessed by quantitative reverse-transcriptase polymerase chain reaction. Among the H. pylori-positive mucosa, 17 out of 29 miRNAs had significant correlations with at least one of the four proinflammatory cytokines in expression. Among the 17 miRNAs, 15 were associated with the degree of neutrophil infiltration and, more prominently, the degree of mononuclear cell infiltration, according to the updated Sydney system. Persistent H. pylori infection may affect the mucosal expression profiles of miRNAs via chronic inflammation mediated by proinflammatory cytokines. There were significant positive correlations between certain miRNAs including the microRNA-200 family and IL-1 beta, IL-6, or TNF-alpha mRNA in H. pylori-negative gastric mucosa. Underscoring the causal association between miRNAs and proinflammatory cytokines may provide insights into the pathogenesis of H. pylori-associated gastritis linking to gastric carcinogenesis.
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Enhanced Expression of CXCL13 in Human Helicobacter pylori-Associated Gastritis (共著) Reviewed
Yujiro Nakashima, Hajime Isomoto, Kayoko Matsushima, Akira Yoshida, Toshiyuki Nakayama, Masaaki Nakayama, Junzo Hisatsune, Tatsuki Ichikawa, Fuminaoa Takeshima, TomayoshiHayashi, Kazuhiko Nakao, Toshiya Hirayama, and Shigeru Kohno
Digestive Diseases and Sciences 2011.11
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Enhanced Expression of CXCL13 in Human Helicobacter pylori-Associated Gastritis
Yujiro Nakashima, Hajime Isomoto, Kayoko Matsushima, Akira Yoshida, Toshiyuki Nakayama, Masaaki Nakayama, Junzo Hisatsune, Tatsuki Ichikawa, Fuminao Takeshima, Tomayoshi Hayashi, Kazuhiko Nakao, Toshiya Hirayama, Shigeru Kohno
DIGESTIVE DISEASES AND SCIENCES 56 ( 10 ) 2887 - 2894 2011.10
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Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles where the CXCL13/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans.Using endoscopic biopsies taken from the gastric antrum of 29 subjects infected with Helicobacter pylori and 22 uninfected subjects, mucosal CXCL13 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.The CXCL13 expression levels were significantly more elevated in H. pylori-positive patients than uninfected ones. The CXCL13 expression levels correlated with the degree of chronic gastritis and bacterial colonization. Immunohistochemistry and in vitro infection assay showed that CXCL13 was not produced by the gastric epithelium, but the alpha-smooth muscle antigen expressing mesenchymal cells were the possible source of CXCL13 within H. pylori-infected gastric mucosa. CXCR5 immunostaining was seen in the CD20-positive lymphoid aggregates.The enhanced induction of CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis.
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Helicobacter pylori VacA reduces the cellular expression of STAT3 and pro-survival Bcl-2 family proteins, Bcl-2 and Bcl-XL, leading to apoptosis in gastric epithelial cells (共著) Reviewed
Ayako Matsumoto, Hajime Isomoto, Masaaki Nakayama, Junzo Hisatsune, Yoshito Nishi, Yujiro Nakashima, Kayoko Matsushima, Hisao Kurazono, Kazuhiko Nakao, Toshiya Hirayama, and Shigeru Kohno
Digestive Diseases and Sciences 2011.4
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Helicobacter pylori VacA Reduces the Cellular Expression of STAT3 and Pro-survival Bcl-2 Family Proteins, Bcl-2 and Bcl-X-L, Leading to Apoptosis in Gastric Epithelial Cells
Ayako Matsumoto, Hajime Isomoto, Masaaki Nakayama, Junzo Hisatsune, Yoshito Nishi, Yujiro Nakashima, Kayoko Matsushima, Hisao Kurazono, Kazuhiko Nakao, Toshiya Hirayama, Shigeru Kohno
DIGESTIVE DISEASES AND SCIENCES 56 ( 4 ) 999 - 1006 2011.4
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Helicobacter pylori vacuolating cytotoxin, VacA, stimulates apoptosis via a mitochondria-dependent pathway. VacA induces apoptosis via activation of the pro-apoptotic B-cell lymphoma (Bcl)-2 family proteins, Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), while the implication of such pro-survival Bcl-2 family members as Bcl-2 and Bcl-X-L in the VacA-induced apoptosis remains unknown. Signal transduction and activator of transcription 3 (STAT3) is a pivotal transcription factor that upregulates Bcl-2 and Bcl-X-L.This study was conducted to elicit the implication of STAT3 and pro-survival Bcl-2 and Bcl-X-L in the intrinsic apoptosis.Immunoblot and reverse transcriptase real-time polymerase chain reaction (RT-PCR) were employed to assess the cellular expression of STAT3, Bcl-2, and Bcl-X-L in response to purified VacA in gastric adenocarcinoma cell lines. VacA-induced apoptosis was quantitated morphologically following knockdown by each specific small interfering RNA (siRNA) or in the presence of pharmacological inhibitors.VacA reduced STAT3, Bcl-2, and Bcl-X-L expression in a dose-dependent manner. Knockdown of STAT3, Bcl-2, and Bcl-X-L by siRNA induced apoptosis to a similar extent in the case of sufficient VacA inoculation. The VacA-mediated reduction of STAT3 expression was independent of cellular vacuolization, since a vacuolar-type ATPase inhibitor, bafilomycin A1, did not inhibit VacA-induced reduction of STAT3, Bcl-2, and Bcl-X-L expression. Instead, a c-JUN NH2-terminal kinase (JNK) inhibitor, SP600125, restored the VacA-induced reduction of STAT3 expression to the basal level.VacA-induced apoptosis may be, in part, implicated in the reduction of STAT3 linking to the downregulation of Bcl-2 and Bcl-X-L, in association with JNK activity.
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MicroRNA signatures in Helicobacter pylori-infected gastric mucosa (共著) Reviewed
Kayoko Matsushima, Hajime Isomoto, Naoki Inoue, Toshiyuki Nakayama, Tomayoshi Hayashi, Masaaki Nakayama, Kazuhiko Nakao, Toshiya Hirayama, and Shigeru Kohno
International journal of cancer 2011.1
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Enhanced expression of CCL20 in human Helicobacter pylori-associated gastritis Reviewed
YOSHIDA A
Clin. Immunol. 130 290 - 297 2009.3
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Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway Reviewed
NAKAYAMA M.
J. Biol. Chem. 284 ( 3 ) 1612 - 1619 2009.1
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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Molecular Characterization of Helicobacter pylori VacA Induction of IL-8 in U937 Cells Reveals a Prominent Role for p38MAPK in Activating Transcription Factor-2, cAMP Response Element Binding Protein, and NF-κB Activation (共著) Reviewed
Junzo Hisatsune, Masaaki Nakayama, Hajime Isomoto, Hisao Kurazono, Naofumi Mukaida, Asish K. Mukhopadhyay, Takeshi Azuma, Yoshio Yamaoka, Jan Sap, Eiki Yamasaki, Kinnosuke Yahiro, Joel Moss, and Toshiya Hirayama
The Journal of Immunology 180 ( 7 ) 5017 - 5027 2008.4
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Molecular characterization of Helicobacter pylori VacA induction of IL-8 in U937 cells reveals a prominent role for p38MAPK in activating transcription factor-2, cAMP response element binding protein, and NF-kappa B activation Reviewed
Junzo Hisatsune, Masaaki Nakayama, Hajime Isomoto, Hisao Kurazono, Naofumi Mukaida, Asish K. Mukhopadhyay, Takeshi Azuma, Yoshio Yamaoka, Jan Sap, Eiki Yamasaki, Kinnosuke Yahiro, Joel Moss, Toshiya Hirayama
JOURNAL OF IMMUNOLOGY 180 ( 7 ) 5017 - 5027 2008.4
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Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC IMMUNOLOGISTS
Helicobacterpylori VacA induces multiple effects on susceptible cells, including vacuolation, mitochondrial damage, inhibition of cell growth, and enhanced cyclooxygenase-2 expression. To assess the ability of H. pylori to modulate the production of inflammatory mediators, we examined the mechanisms by which VacA enhanced IL-8 production by promonocytic U937 cells, which demonstrated the greatest VacA-induced IL-8 release of the cells tested. Inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), IKBa ((E)-3-(4-methylphenyisulfonyl)-2-propenenitrile), Ca2+ entry (SKF96365), and intracellular Ca 21 channels (dantrolene) blocked VacA-induced IL-8 production. Furthermore, an intracellular Ca2+ chelator (BAPTA-AM), which inhibited VacA-activated p38 MAPK, caused a dose-dependent reduction in VacA-induced IL-8 secretion by U937 cells, implying a role for intracellular Ca 21 in mediating activation of MAPK and the canonical NF-kappa B pathway. VacA stimulated translocation of NF-kappa Bp65 to the nucleus, consistent with enhancement of IL-8 expression by activation of the NF-kappa B pathway. In addition, small interfering RNA of activating transcription factor (ATF)-2 or CREB, which is a p38MAPK substrate and binds to the AP-1 site of the IL-8 promoter, inhibited VacA-induced IL-8 production. VacA activated an IL-8 promoter containing an NF-IL-6 site, but not a mutated AP-1 or NF-kappa B site, suggesting direct involvement of the ATF-2/CREB binding region or NF-kappa B-binding regions in VacA-induced IL-8 promoter activation. Thus, in U937 cells, VacA directly increases IL-8 production by activation of the p38 MAPK via intracellular Ca2+ release, leading to activation of the transcription factors, ATF-2, CREB, and NF-kappa B.
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Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells
Junzo Hisatsune, Eiki Yamasaki, Masaaki Nakayama, Daisuke Shirasaka, Hisao Kurazono, Yohtaro Katagata, Hiroyasu Inoue, Jiahuai Han, Jan Sap, Kinnosuke Yahiro, Joel Moss, Toshiya Hirayama
Infection and Immunity 75 ( 9 ) 4472 - 4481 2007.9
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Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase 2 (COX-2) mRNA in a time- and dose-dependent manner. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erk1/2 cascade, partially suppressed the increase. Consistent with involvement of p38 MAPK, VacA-induced accumulation of COX-2 mRNA was reduced in AZ-521 cells overexpressing a dominant-negative p38 MAPK (DN-p38). Phosphatidylinositol- specific phospholipase C, which inhibits VacA-induced p38 MAPK activation, blocked VacA-induced COX-2 expression. In parallel with COX-2 expression, VacA increased prostaglandin E2 (PGE2) production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE 2 production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-κB or NF-interleukin-6 sites but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2 promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-small interfering RNA duplexes resulted in suppression of COX-2 expression. Thus, VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
DOI： 10.1128/IAI.00500-07
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Helicobacter pylori VacA enhances PGE2 production through induction of COX-2 expression via a p38 MAP kinase/ ATF-2 cascade in AZ-521 cells (共著) Reviewed
Junzo Hisatsune, Eiki Yamasaki, Masaaki Nakayama, Daisuke Shirasaka, Hisao Kurazono, Yohtaro Katagata, Hiroyasu Inoue, Jiahuai Han, Jan Sap, Kinnosuke Yahiro, Joel Moss, and Toshiya Hirayama
Infection and Immunity 75 ( 9 ) 4472 - 4481 2007.6
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Helicobacter pylori VacA clustering in lipid rafts, mediated by its receptor, RPTPβ, is required for VacA-induced vacuolation in AZ-521 cells. Reviewed
Masaaki Nakayama, Akihiro Wada, Junzo Hisatsune, Eiki Yamasaki, Yoshito Nishi, Kinnosuke Yahiro, Hisao Kurazono, Joel Moss, and Toshiya Hirayama
Infection and Immunity 74 ( 12 ) 6571 - 6580 2006.12
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Eiki Yamasaki, Akihiro Wada, Atsushi Kumatori, Ichiro Nakagawa, Junko Funao, Masaaki Nakayama, Junzo Hisatsune, Miyuki Kimura, Joel Moss, Toshiya Hirayama
Journal of Biological Chemistry 281 ( 16 ) 11250 - 11259 2006.4
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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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[Structure and intoxication of VacA].
Toshiya Hirayama, Akihiro Wada, Masaaki Nakayama, Yoshito Nishi, Jyunzo Hisatsune
Nihon rinsho. Japanese journal of clinical medicine 63 Suppl 11 53 - 7 2005.11
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Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA. Reviewed International journal
Blanquita B De Guzman, Junzo Hisatsune, Masaaki Nakayama, Kinnosuke Yahiro, Akihiro Wada, Eiki Yamasaki, Yoshito Nishi, Shiho Yamazaki, Takeshi Azuma, Yoshiyuki Ito, Masahiro Ohtani, Thea van der Wijk, Jeroen den Hertog, Joel Moss, Toshiya Hirayama
Cellular microbiology 7 ( 9 ) 1285 - 1293 2005.9
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Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPalpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTPalpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA.
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Essential domain of receptor tyrosine phosphatase beta (RPTPbeta) for interaction with Helicobacter pylori vacuolating cytotoxin. Reviewed International journal
Kinnosuke Yahiro, Akihiro Wada, Eiki Yamasaki, Masaaki Nakayama, Yoshito Nishi, Jyunzou Hisatsune, Naoko Morinaga, Jan Sap, Masatoshi Noda, Joel Moss, Toshiya Hirayama
The Journal of biological chemistry 279 ( 49 ) 51013 - 51021 2004.12
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Helicobacter pylori produces a potent exotoxin, VacA, which causes progressive vacuolation as well as gastric injury. Although VacA was able to interact with two receptor-like protein tyrosine phosphatases, RPTPbeta and RPTPalpha, RPTPbeta was found to be responsible for gastric damage caused by VacA. To define the region of RPTPbeta involved in VacA binding, we made mutants of human cDNA RPTPbeta-B, a short receptor form of RPTPbeta. Immunoprecipitation experiments to assess VacA binding to RPTPbeta-B mutants indicated that five residues (QTTQP) at positions 747-751 of the extracellular domain of RPTPbeta-B (which is commonly retained in RPTPbeta-A, a long form of RPTPbeta) play a crucial role in its interaction with VacA, resulting in vacuolation as well as Git-1 phosphorylation. Transfected cells expressing deletion mutant Delta752, which lacks QTTQP, or the double point mutant Delta747 (T748A,T749A) had diminished vacuolation in response to VacA. Treatment of RPTPbeta-B and Delta747 (which have QTTQP at 747-751) with neuraminidase and O-glycosidase diminished their VacA binding, whereas chondroitinase ABC did not have an effect. No inhibitory effect of pleiotrophin, a natural RPTPbeta ligand, on VacA binding to RPTPbeta-B or Delta747 was observed, supporting the conclusion that the extracellular region of RPTPbeta-B responsible for VacA binding is different from that involved in binding pleiotrophin. These data define the region in the RPTPbeta extracellular domain critical for VacA binding, in particular the sequence QTTQP at positions 747-751 with crucial threonines at positions 748 and 749 and are consistent with a role for terminal sialic acids possibly because of threonine glycosylation.
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Ken-ichi Ogushi, Akihiro Wada, Takuro Niidome, Tatsuya Okuda, Rafael Llanes, Masaaki Nakayama, Yoshito Nishi, Hisao Kurazono, Kelly D. Smith, Alan Aderem, Joel Moss, Toshiya Hirayama
Journal of Biological Chemistry 279 ( 13 ) 12213 - 12219 2004.3
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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Helicobacter pylori VacA activates the p38/activating transcription factor 2-mediated signal pathway in AZ-521 cells. Reviewed International journal
Masaaki Nakayama, Miyuki Kimura, Akihiro Wada, Kinnosuke Yahiro, Ken-ichi Ogushi, Takuro Niidome, Akihiro Fujikawa, Daisuke Shirasaka, Nobuo Aoyama, Hisao Kurazono, Masaharu Noda, Joel Moss, Toshiya Hirayama
The Journal of biological chemistry 279 ( 8 ) 7024 - 7028 2004.2
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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Persistent Helicobacter pylori colonization in the stomach induces gastritis and peptic ulcer and interferes with ulcer healing. Most strains of H. pylori produce a cytotoxin, VacA, that induces cytoplasmic vacuolation in epithelial cells with structural and functional changes, leading to gastric injury. VacA is known to cause cell death by mitochondrial damage. We hypothesized that VacA might disrupt other signaling pathways; to that end, we examined the effects of VacA on MAPKs to elucidate their role in the abnormalities seen in VacA-treated cells. VacA stimulated phosphorylation of p38 and Erk1/2, but not JNK, in AZ-521 cells. Both phosphorylation and kinase activation of p38 were maximal 10-30 min after addition of VacA and declined thereafter. Treatment with anti-VacA antibody or the p38 inhibitor SB203580 blocked p38 phosphorylation caused by VacA and inhibited VacA-induced phosphorylation of activating transcription factor 2 (ATF-2), which is implicated in transcriptional control of stress-responsive genes. These data indicate that VacA stimulates a p38/ATF-2-mediated signal pathway. However, 10 microM SB203580, which is sufficient to decrease p38 phosphorylation, did not inhibit VacA-induced cellular vacuolation, decrease in mitochondrial membrane potential, or cytochrome c release from mitochondria. These results suggest that VacA-induced activation of p38/ATF-2-mediated signal pathway is independent of cellular vacuolation, decrease in mitochondrial membrane potential, or cytochrome c release from mitochondria caused by VacA. The cytotoxin may thus act independently on several cellular targets, leading to disruption of signaling, regulatory, and metabolic pathways.
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Protein-tyrosine Phosphatase α, RPTPα, Is a Helicobacter pylori VacA Receptor Reviewed
Kinnosuke Yahiro, Akihiro Wada, Masaaki Nakayama, Takahiro Kimura, Ken-ichi Ogushi, Takuro Niidome, Haruhiko Aoyagi, Ken-ichi Yoshino, Kazuyoshi Yonezawa, Joel Moss, Toshiya Hirayama
Journal of Biological Chemistry 278 ( 21 ) 19183 - 19189 2003.5
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KIMURA Takahiro, WADA Akihiro, NAKAYAMA Masaaki, OGUSHI Ken-ichi, NISHI Yoshito, DE GUZMAN Blanquita B., MOSS Joel, HIRAYAMA Toshiya
Microbiology and Immunology 47 ( 1 ) 105 - 107 2003.1
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Other Link： http://search.jamas.or.jp/link/ui/2003196659
Books
Books
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「Precision Medicine1月号（2024年1/25発刊）歯根膜由来細胞シートによる歯周組織再生治療」研究者の最新動向ー歯周病菌のプロテアーゼの宿主作用能と歯周組織炎症における可能性
（ Role： Contributor）
株式会社北隆館 2024.1
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Pathogenic role of cysteine proteases produced by periodontal pathogen Porphyromonas gingivitis in periodontal disease
（ Role： Contributor）
2023.9
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「アレルギーの臨床2月号（1/25発刊）アレルギー疾患とマイクロバイオーム」口腔細菌叢と疾患ー口腔細菌の病原因子による歯周疾患への影響
中山真彰（ Role： Sole author）
株式会社北隆館 2019.1
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「2018年別冊BIO Clinica春20号（9/25刊）口腔疾患と慢性炎症」
中山真彰（ Role： Sole author）
株式会社北隆館 2018.9
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月刊細胞 口腔疾患のサイエンス
（ Role： Sole author）
ニューサイエンス社 2018.8
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月刊 地域ケアリング
（ Role： Sole author）
株式会社北隆館 2018.6
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月刊細胞 病原性細菌の制御
（ Role： Sole author）
ニューサイエンス社 2017.9
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MISC
MISC
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Porphyromonas gingivalis感染におけるPLCを介した細胞内カルシウム流入による歯周組織炎症への影響
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
日本細菌学雑誌 79 ( 2 ) 111 - 111 2024.6
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研究者の最新動向 歯周病菌のプロテアーゼの宿主作用能と歯周組織炎症における可能性
中山 真彰
Precision Medicine 7 ( 1 ) 60 - 63 2024.1
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Language：Japanese Publisher：(株)北隆館
歯周病は歯周組織に起こる炎症性疾患であり,デンタルプラークと関連した細菌感染症である。なかでも歯周病原細菌Porphyromonas gingivalisの歯周疾患への関与については多く研究されており,本菌が産生するプロテアーゼ"ジンジパイン"は病原因子として歯周病の病態形成に強く関与すると考えられる。本稿では,ジンジパインによる歯周組織傷害と炎症応答のメカニズムを紹介する。(著者抄録)
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The possibility between pathogenicity of periodontal disease bacterial proteases and inflammation of periodontal tissues
中山真彰
月刊Precision Medicine 7 ( 1 ) 2024
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Virulence functions of cysteine proteases from Porphyromonas gingivalis in periodontal inflammation
中山真彰
Bio Clinica 39 ( 13 ) 2024
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歯周病における歯周病菌が産生するプロテアーゼの病原的役割—Pathogenic role of cysteine proteases produced by periodontal pathogen Porphyromonas gingivalis in the periodontal disease
中山 真彰
アグリバイオ = Agricultural biotechnology 7 ( 10 ) 897 - 900 2023.9
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Porphyromonas gingivalisジンジパインによるphospholipase Cの活性化と歯周組織の炎症との関連性
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
Journal of Oral Biosciences Supplement 2023 [P3 - 32] 2023.9
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Porphyromonas gingivalisジンジパインによるPLCを介したCOX-2発現とPGE2産生の分子機序
中山 真彰, 山口 智之, 内藤 真理子, 中山 浩次, 大原 直也
日本細菌学雑誌 78 ( 1 ) 88 - 88 2023.2
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Porphyromonas gingivalis gingipains induce COX-2 expression and PGE2 production via phospholipase C
中山真彰, 中山真彰, 山口智之, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 78 ( 1 ) 2023
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Pathogenic role of cysteine proteases produced by periodontal pathogen Porphyromonas gingivalis in the periodontal disease
中山真彰
アグリバイオ 7 ( 10 ) 2023
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新規除鉄剤スーパーポリフェノール(SP)を応用した新規口腔感染制御システムの構築
伊東有希, 大森一弘, 伊東孝, 中山真彰, 池田淳史, 大原利章, 高柴正悟
日本鉄バイオサイエンス学会学術集会プログラム・抄録集 47th 2023
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Porphyromonas gingivalisジンジパインによるphospholipase Cの活性化と歯周組織の炎症との関連性
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2023 2023
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Pathogenic role of cysteine proteases produced by periodontal pathogen Porphyromonas gingivalis in the periodontal disease
中山真彰
アグリバイオ 7 ( 10 ) 2023
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Relationship between CX3CL1 and lymph node metastasis in oral cancer
河合穂高, トゥ シュ エイン, 中山真彰, 大原利章, 長塚仁
日本癌学会学術総会抄録集(Web) 82nd 2023
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Drug development for drug-resistant tuberculosis and the non-tuberculous mycobacterial disease
瀧井猛将, 瀧井猛将, 岩月正人, 山口智之, 君嶋葵, 渡邊善行, 中山真彰, 大原直也, 浅見行弘
日本薬学会年会要旨集(Web) 143rd 2023
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Porphyromonas gingivalisジンジパインによるCOX-2発現とPGE2産生におけるホスホリパーゼの役割(The role of phospholipase on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production)
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
Journal of Oral Biosciences Supplement 2022 219 - 219 2022.9
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口腔癌におけるCX3CL1の影響
トゥ・シュ・エイン, 河合 穂高, 中山 真彰, メイ・ワトウ, 伏見 滋子, 中野 敬介, 飯田 征二, 長塚 仁
日本病理学会会誌 111 ( 1 ) 278 - 278 2022.3
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Lautropia mirabilisの分離・培養および検出法の確立と分離株の薬剤感受性に関する解析
佐藤 あやめ, 中山 真彰, 藤井 伸治, 松岡 賢市, 前田 嘉信, 和田 崇之, 曽我 賢彦, 大原 直也
日本細菌学雑誌 77 ( 1 ) 61 - 61 2022.2
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16S rRNA遺伝子の513シトシン挿入変異を有するストレプトマイシン依存性Mycobacterium bovis BCG株(Streptomycin dependent Mycobacterium bovis BCG possessing a 513 cytosine insertion in 16S rRNA gene)
本田 尚子, 佐藤 法仁, 中山 真彰, 松村 隆之, 関塚 剛史, 黒田 誠, 阿戸 学, 小林 和夫, 石井 孝司, 大原 直也
日本細菌学雑誌 77 ( 1 ) 112 - 112 2022.2
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Porphyromonas gingivalisジンジパインによるCOX-2発現とPGE2産生におけるカルシウムチャネルの役割
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
日本細菌学雑誌 77 ( 1 ) 86 - 86 2022.2
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侵襲性歯周炎の血液診断マーカー候補となる細胞外小胞由来マイクロRNAとその炎症誘導機構の探索
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日本歯周病学会会誌(Web) 64 2022
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The role of phospholipase on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2022 2022
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Investigation of CX3CL1 involvement to oral cancer
HTOO Shwe Eain, HTOO Shwe Eain, 河合穂高, 中山真彰, MAY Wathone Oo, 伏見滋子, 中野敬介, 飯田征二, 長塚仁
日本病理学会会誌 111 ( 1 ) 2022
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Role of calcium channels in COX-2 expression and PGE2 production by gingipains
中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 77 ( 1 ) 2022
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Isolation and detection methods for Lautropia mirabilis and analysis of drug susceptibility
佐藤あやめ, 佐藤あやめ, 中山真彰, 藤井伸治, 松岡賢市, 前田嘉信, 和田崇之, 曽我賢彦, 大原直也
日本細菌学雑誌(Web) 77 ( 1 ) 2022
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カルシウムチャネルを介したPorphyromonas gingivalisジンジパインによるCOX-2発現の分子機序(The molecular mechanism of Porphyromonas gingivalis gingipains-induced COX-2 expression via the calcium channels)
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
Journal of Oral Biosciences Supplement 2021 285 - 285 2021.10
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新たな視点から口腔内細菌を見つめる-個々の病原体から菌叢解析まで- P.gingivalisジンジパインによるCOX-2発現における細胞外カルシウム流入の重要性
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
日本細菌学雑誌 76 ( 1 ) 50 - 50 2021.2
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The significance of calcium influx on COX-2 expression induced by P. gingivalis gingipains
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 76 ( 1 ) 2021
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フッ化ナトリウムによるCCNファミリー遺伝子制御を介した歯肉線維化抑制作用の検討
水川朋美, 水川朋美, 西田崇, 西田崇, 明石翔, 大杉綾花, 大杉綾花, 大森一弘, 大森一弘, 中山真彰, 中山真彰, 高柴正悟, 上岡寛, 滝川正春, 久保田聡
岡山歯学会雑誌 40 ( 2 ) 2021
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P.gingivalisジンジパインによるCOX-2発現と細胞外カルシウム流入の分子機序
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
Journal of Oral Biosciences Supplement 2020 219 - 219 2020.9
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16S rRNA遺伝子の513シトシン挿入変異を有するストレプトマイシン依存性Mycobacterium bovis BCG株(Streptomycin dependent Mycobacterium bovis BCG possessing a 513 cytosine insertion in 16S rRNA gene)
本田 尚子, 佐藤 法仁, 中山 真彰, 松村 隆之, 関塚 剛史, 黒田 誠, 阿戸 学, 小林 和夫, 石井 孝司, 大原 直也
日本細菌学雑誌 75 ( 1 ) 154 - 154 2020.1
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P.gingivalisジンジパイン誘導性COX-2発現における細胞外カルシウム流入の関与
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
日本細菌学雑誌 75 ( 1 ) 88 - 88 2020.1
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Development of a culture method and a PCR-based method for detection of Lautropia mirabilis.
佐藤あやめ, 佐藤あやめ, 中山真彰, 中山真彰, 中川美緒, 小崎弘貴, 室美里, 曽我賢彦, 大原直也, 大原直也
日本細菌学雑誌(Web) 75 ( 1 ) 2020
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The involvement of calcium inflax on P. gingivalis gingipains-induced COX-2 expression
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 75 ( 1 ) 2020
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The molecular mechanism between COX-2 expression and calcium influx by P. gingivalis gingipains
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2020 2020
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健常者口腔内からのLautropia mirabilisの分離とL.mirabilis検出方法の確立
佐藤 あやめ, 中山 真彰, 中川 美緒, 小崎 弘貴, 室 美里, 曽我 賢彦, 大原 直也
岡山歯学会雑誌 38 ( 2 ) 84 - 84 2019.12
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Terrein類縁体の抗腫瘍効果に関する研究
廣瀬 泰良, 伊原木 聰一郎, 大森 一弘, 中山 真彰, 佐々木 朗
岡山歯学会雑誌 38 ( 2 ) 91 - 91 2019.12
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健常者口腔内からのLautropia mirabilisの分離とL.mirabilis検出方法の確立
佐藤 あやめ, 中山 真彰, 中川 美緒, 小崎 弘貴, 室 美里, 曽我 賢彦, 大原 直也
岡山歯学会雑誌 38 ( 2 ) 84 - 84 2019.12
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Porphyromonas gingivalisのPGN_0297の機能解析
小野 晋太郎, 中山 真彰, 大原 直也, 高柴 正悟
日本歯周病学会会誌 61 ( 秋季特別 ) 124 - 124 2019.10
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Porphyromonas gingivalis PGN_0296オペロンの解析
小野 晋太郎, 中山 真彰, A Shahriar, 大原 直也
Journal of Oral Biosciences Supplement 2019 291 - 291 2019.10
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Porphyromonas gingivalis gingipainsによるCOX2発現とPGE2産生における細胞内カルシウムの関与
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
Journal of Oral Biosciences Supplement 2019 275 - 275 2019.10
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非結核性抗酸菌におけるpYT系プラスミド利用の可能性
野崎 高儀, 中山 真彰, 小川 みどり, 吉田 志緒美, 阿戸 学, 大原 直也
日本細菌学雑誌 74 ( 1 ) 88 - 88 2019.3
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非結核性抗酸菌におけるpYT系プラスミド利用の可能性
野崎 高儀, 中山 真彰, 小川 みどり, 吉田 志緒美, 阿戸 学, 大原 直也
日本細菌学雑誌 74 ( 1 ) 88 - 88 2019.3
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急速に増殖するMycobacterium aviumの亜種のhominissuis 104株の分析(Analysis of a rapid growing Mycobacterium avium subspecies hominissuis 104 strain)
河喜多 智美, 吉田 光範, 鈴木 仁人, 中田 登, 瀧井 猛将, 中山 真彰, 梁 明秀, 星野 仁彦, 阿戸 学, 大原 直也
日本細菌学雑誌 74 ( 1 ) 61 - 61 2019.3
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病原因子Zmp1欠損マイコバクテリアによるT細胞免疫応答への影響
梅村正幸, 梅村正幸, 梅村正幸, 藏根友美, 中山真彰, 大原直也, 高江洲義一, 高江洲義一, 高江洲義一, 松崎吾朗, 松崎吾朗, 松崎吾朗
日本インターフェロン・サイトカイン学会学術集会抄録集 84th 2019
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健常者口腔内からのLautropia mirabilisの分離とL.mirabilis検出方法の確立
佐藤あやめ, 佐藤あやめ, 中山真彰, 中山真彰, 中川美緒, 小崎弘貴, 室美里, 曽我賢彦, 大原直也, 大原直也
岡山歯学会雑誌 38 ( 2 ) 84 - 84 2019
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Terrein類縁体の抗腫瘍効果に関する研究
廣瀬泰良, 伊原木聰一郎, 大森一弘, 中山真彰, 佐々木朗
岡山歯学会雑誌 38 ( 2 ) 91 - 91 2019
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Porphyromonas gingivalis gingipainsによるCOX2発現とPGE2産生における細胞内カルシウムの関与
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2019 2019
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pYTプラスミドの非結核性抗酸菌における応用の可能性の検討
野崎高儀, 野崎高儀, 中山真彰, 中山真彰, 小川みどり, 吉田志緒美, 阿戸学, 大原直也, 大原直也
結核 94 ( 3 ) 2019
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Porphyromonas gingivalis PGN_0296オペロンの解析
小野晋太郎, 中山真彰, SHAHRIAR A, 大原直也
Journal of Oral Biosciences Supplement (Web) 2019 2019
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マイコバクテリア病原因子Zmp1の自然免疫およびT細胞免疫応答への影響
梅村正幸, 梅村正幸, 木村倫和, 岩橋晃平, 藏根友美, 照屋尚子, 中山真彰, 大原直也, 高江洲義一, 高江洲義一, 松崎吾朗, 松崎吾朗
日本熱帯医学会大会プログラム抄録集 60th 2019
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Porphyromonas gingivalisのPGN_0297の機能解析
小野晋太郎, 中山真彰, 大原直也, 高柴正悟
日本歯周病学会会誌(Web) 61 2019
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The role of Ca2+ on Porphyromonas gingivalis gingipains-induced COX-2 expression
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 74 ( 1 ) 2019
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The possibility of the pYT plasmid in the use of genetic analysis of NTM
野崎高儀, 野崎高儀, 中山真彰, 小川みどり, 吉田志緒美, 阿戸学, 大原直也
日本細菌学雑誌(Web) 74 ( 1 ) 2019
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Terrein類縁体の抗腫瘍効果に関する研究
廣瀬泰良, 伊原木聰一郎, 大森一弘, 中山真彰, 佐々木朗
岡山歯学会雑誌 38 ( 2 ) 2019
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The pathogenic mechanism of p. gingivalis gingipains on periodontitis
50 ( 10 ) 542 - 544 2018.9
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福祉の現場から 歯周病菌が産生するプロテアーゼの歯周疾患における重要性
中山 真彰
地域ケアリング 20 ( 7 ) 62 - 65 2018.7
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BCGの増殖率促進に関与する遺伝子の調査(Investigation of genes involved in promoting the growth rate of BCG)
竜門 亜矢子, 中山 真彰, 和田 崇之, 橘 理人, 阿戸 学, 中島 千絵, 鈴木 定彦, 小崎 弘貴, 大原 直也
日本細菌学雑誌 73 ( 1 ) 68 - 68 2018.2
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Porphyromonas gingivalis gingipainsによるMEK/ERK/AP-1およびIKK/NF-kBp65の活性化を介したCOX-2発現およびPGE2産生の誘導機構
中山真彰, 中山真彰, 内藤真理子, 橘理人, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2018 2018
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Investigation of genes involved in promoting the growth rate of BCG
竜門亜矢子, 中山真彰, 中山真彰, 和田崇之, 橘理人, 阿戸学, 中島千絵, 鈴木定彦, 小崎弘貴, 大原直也, 大原直也
日本細菌学雑誌(Web) 73 ( 1 ) 2018
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Porphyromonas gingivalisジンジパインによるCOX-2発現誘導を介したPGE2産生の分子解析
中山真彰, 中山真彰, 内藤真理子, 橘理人, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 73 ( 1 ) 2018
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BCG Rv3405cによるRv3406の遺伝子発現抑制機構の解析
白崎かおり, 白崎かおり, 中山真彰, 橘理人, 山本三郎, 瀧井猛将, 岡部真裕子, 阿戸学, 上岡寛, 大原直也
日本細菌学雑誌(Web) 73 ( 1 ) 2018
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Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on periodontal diseases. International journal
Masaaki Nakayama, Naoya Ohara
The Japanese dental science review 53 ( 4 ) 134 - 140 2017.11
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Porphyromonas gingivalis (P. gingivalis) is a major oral pathogen and associated with periodontal diseases including periodontitis and alveolar bone loss. In this review, we indicate that two virulence factors, which are hemoglobin receptor protein (HbR) and cysteine proteases "gingipains", expressed by P. gingivalis have novel functions on the pathogenicity of P. gingivalis. P. gingivalis produces three types of gingipains and concomitantly several adhesin domains. Among the adhesin domains, hemoglobin receptor protein (HbR), also called HGP15, has the function of induction of interleukin-8 (IL-8) expression in human gingival epithelial cells, indicating the possibility that HbR is associated with P. gingivalis-induced periodontal inflammation. On bacteria-host cells contact, P. gingivalis induces cellular signaling alteration in host cells. Phosphatidylinositol 3-kinase (PI3K) and Akt are well known to play a pivotal role in various cellular physiological functions including cell survival and glucose metabolism in mammalian cells. Recently, we demonstrated that gingipains attenuate the activity of PI3K and Akt, which might have a causal influence on periodontal diseases by chronic infection to the host cells from the speculation of molecular analysis. In this review, we discuss new molecular and biological characterization of the virulence factors from P. gingivalis.
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The virulence of P. gingivalis gingipains on periodontal diseases
49 ( 11 ) 568 - 571 2017.10
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Porphyromonas gingivalisジンジパインによるCOX-2発現とPGE2産生の分子機序
中山真彰, 中山真彰, 橘理人, 橘理人, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2017 2017
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PDIM/PGLはBCGの胆汁酸に対する抵抗性に関与する
田村庄平, 中山真彰, 藤原永年, 和田崇之, 山本三郎, 小崎弘貴, 飯田征二, 大原直也
日本細菌学雑誌(Web) 72 ( 1 ) 2017
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歯周病におけるP.gingivalisジンジパインの重要性
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 72 ( 1 ) 2017
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BCG ThyA,ThyX変異株の解析
竜門亜矢子, 中山真彰, 橘理人, 小崎弘貴, 大原直也
Journal of Oral Biosciences Supplement (Web) 2017 2017
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Porphyromonas gingivalisジンジパインによるPGE2産生の分子機序
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌(Web) 72 ( 1 ) 2017
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非結核性抗酸菌(non-tuberculous mycobacteria,NTM)の薬剤排出能に関する検討
小崎弘貴, 中山真彰, 橘理人, 大原直也
Journal of Oral Biosciences Supplement (Web) 2017 2017
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BCG Tokyo RD16領域に存在するJTY_3475cはJTY_3476の遺伝子発現を負に制御する
白崎かおり, 中山真彰, 山本三郎, 瀧井猛将, 岡部真裕子, 阿戸学, 上岡寛, 大原直也
日本細菌学雑誌(Web) 72 ( 1 ) 2017
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大原 直也, 阿戸 学, 鈴木 定彦, 小林 和夫, 有村 友紀, 中山 真彰, 中島 千絵, 妹尾 昌紀, 田川 淳平, 中山 浩次
結核 91 ( 3 ) 325 - 325 2016.3
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抗酸菌のPAS耐性機序の解明 BCG thyX欠損株および過剰発現株の作製
有村 友紀, 中山 真彰, 妹尾 昌紀, 田川 淳平, 阿戸 学, 中島 千絵, 鈴木 定彦, 中山 浩次, 小林 和夫, 大原 直也
日本細菌学雑誌 71 ( 1 ) 142 - 142 2016.2
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PI3K/Akt経路に対するP.gingivalisジンジパインの役割
中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2016 2016
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プロテオーム解析法を用いた未分化能を有する歯肉上皮系前駆細胞における歯周病菌産生毒素の標的膜タンパク質の探索
中山真彰
Institute for Fermentation, Osaka. Research Communications ( 30 ) 2016
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ポルフィロモナス・ジンジバリスが産生するジンジパインによるPI3キナーゼ/Akt経路抑制の分子機序
中山真彰, 中山真彰
Journal of Oral Biosciences Supplement (Web) 2016 2016
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BCGにおけるcyclic-di-GMP菌体内合成の影響
妹尾昌紀, 中山真彰, 有村友紀, 飯田征二, 大原直也, 飯田征二, 大原直也
Journal of Oral Biosciences Supplement (Web) 2015 2015
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BCG thyX欠損株の作製とその性状解析
有村友紀, 中山真彰, 妹尾昌紀, 田川淳平, 中山浩次, 飯田征二, 大原直也, 大原直也
Journal of Oral Biosciences Supplement (Web) 2015 2015
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Porphyromonas gingivalis ATCC33277株におけるRpoNの性状解析
加野小奈美, 中山真彰, 中山真彰, 田川淳平, 白崎かおり, 上岡寛
日本矯正歯科学会大会プログラム・抄録集 74th 2015
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歯周病原細菌の感染による免疫応答と破骨細胞分化制御の相関性
中山真彰, 中山真彰, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌 70 ( 1 ) 2015
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細菌感染による破骨細胞分化への自然免疫応答の重要性
中山真彰, 中山真彰, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌 70 ( 1 ) 2015
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Porphyromonas gingivalis ATCC 33277株rpoN低発現株の性状解析
加野小奈美, 井上哲圭, 田口裕子, 田川淳平, 中山真彰, 内藤真理子, 中山浩次, 大原直也
日本細菌学雑誌 70 ( 1 ) 2015
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抗酸菌におけるパラアミノサリチル酸に対する新たな耐性機序の可能性
ZHAO Na, 中山真彰, 関塚剛史, 黒田誠, 本田尚子, 阿戸学, 中島千絵, 鈴木定彦, 大原直也
日本細菌学雑誌 70 ( 1 ) 2015
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Porphyromonas gingivalisの表層蛋白質の修飾と機能に関与する分子の解析
田口裕子, 佐藤啓子, 雪竹英治, 井上哲圭, 井上哲圭, 中山真彰, 中山真彰, 内藤真理子, 中山浩次, 大原直也, 大原直也
日本細菌学雑誌 70 ( 1 ) 2015
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P.gingivalisジンジパインによるPI3K/Akt経路の抑制効果とその意義
中山真彰, 内藤真理子, 中山浩次, 大原直也
Journal of Oral Biosciences Supplement (Web) 2015 2015
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Porphyromonas gingivalisにおける菌体外のジンジパインの酵素活性に関わる新規遺伝子について
田口裕子, 井上哲圭, 佐藤啓子, 加野小奈美, 中山真彰, 内藤真理子, 中山浩次, 大原直也
Journal of Oral Biosciences Supplement (Web) 2014 2014
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細菌感染による免疫応答が破骨細胞分化に与える影響
中山真彰, 井上哲圭, 中山浩次, 大原直也
Journal of Oral Biosciences Supplement (Web) 2014 2014
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口腔癌細胞株担癌マウスに対するBCG生菌と5-FU併用療法による延命効果の検討
村上純, 大原直也, 中山真彰, 辻極秀次, 長塚仁, 此内浩信, 柳文修, 苔口進, 久富美紀, 藤田麻里子, 畦坪輝寿, 浅海淳一
日本癌治療学会学術集会(CD-ROM) 52nd 2014
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Porphyromonas gingivalisではsigma-54をコードするPGN_1202(rpoN)は必須遺伝子である
加野小奈美, 井上哲圭, 田口裕子, 中山真彰, 内藤真理子, 中山浩次, 大原直也
日本細菌学雑誌 69 ( 1 ) 2014
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Porphyromonas gingivalis PGN1796変異株の細胞内侵入性および薬剤感受性
田口裕子, 井上哲圭, 佐藤啓子, 加野小奈美, 中山真彰, 中山浩次, 大原直也
日本細菌学雑誌 69 ( 1 ) 2014
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P.gingivalisジンジパインのタンパク分解作用によるPI3K/Akt経路への影響
中山真彰, 井上哲圭, 中山浩次, 大原直也
日本細菌学雑誌 69 ( 1 ) 2014
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異所性感染および全身疾患に対する歯周病原細菌の病原性の理解
中山真彰, 大原直也
日本臨床腸内微生物学会誌 16 ( 1 ) 2014
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Porphyromonas gingivalisの薬剤排出ポンプ欠損株の薬剤感受性と細胞内侵入性
井上哲圭, 井上哲圭, 田口裕子, 加野小奈美, 中山真彰, 黒田照夫, 大原直也, 大原直也
日本細菌学雑誌 69 ( 1 ) 2014
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口腔癌に対するBCG生菌療法による抗腫瘍、延命効果の検討
村上 純, 大原 直也, 中山 真彰, 辻極 秀次, 長塚 仁, 此内 浩信, 柳 文修, 畦坪 輝寿, 浅海 淳一
Journal of Oral Biosciences Supplement 2013 222 - 222 2013.9
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Porphyromonas gingivalisのPGN_1202(rpoN)は必須遺伝子である
加野 小奈美, 井上 哲圭, 田口 裕子, 田川 淳平, 中山 真彰, 山城 隆, 大原 直也
Journal of Oral Biosciences Supplement 2013 169 - 169 2013.9
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Porphyromonas gingivalisの薬剤排出ポンプ様分子をコードする遺伝子
井上哲圭, 田口裕子, 加野小奈美, 中山真彰, 大原直也
Journal of Oral Biosciences Supplement (Web) 2013 2013
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Porphyromonas gingivalis PGN_1796は薬剤感受性に関与する
田口裕子, 佐藤啓子, 井上哲圭, 加野小奈美, 中山真彰, 前田博史, 中山浩次, 大原直也
Journal of Oral Biosciences Supplement (Web) 2013 2013
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口腔癌に対するBCG生菌療法による抗腫瘍,延命効果の検討
村上純, 大原直也, 中山真彰, 辻極秀次, 長塚仁, 此内浩信, 柳文修, 畦坪輝寿, 浅海淳一
Journal of Oral Biosciences Supplement (Web) 2013 2013
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Porphyromonas gingivalisのPGN_1202(rpoN)は必須遺伝子である
加野小奈美, 井上哲圭, 田口裕子, 田川淳平, 中山真彰, 山城隆, 大原直也
Journal of Oral Biosciences Supplement (Web) 2013 2013
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Porphyromonas gingivalisにおいて電気穿孔法で導入可能なプラスミドベクターの構築
田川淳平, 井上哲圭, 佐藤啓子, 内藤真理子, 中山真彰, 中山浩次, 山城隆, 大原直也
Journal of Oral Biosciences Supplement (Web) 2013 2013
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国際共同基盤研究に応用する抗酸菌感染症研究の整備 宿主への侵入および宿主内生存に関わる抗酸菌の分子と宿主要因に関する研究
大原直也, 小林和夫, 中山真彰, 井上哲圭
国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成24年度 総括・分担研究報告書 2013
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Porphyromonas gingivalisにおける薬剤排出ポンプ様遺伝子破壊株の薬剤感受性
井上哲圭, 中山真彰, 大原直也
日本細菌学雑誌 68 ( 1 ) 2013
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P.gingivalisジンジパインによるPI3K/Akt経路の抑制機序
中山真彰, 井上哲圭, 内藤真理子, 中山浩次, 大原直也
日本細菌学雑誌 68 ( 1 ) 2013
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P.gingivalisジンジパインによるPI3K/Akt経路の抑制機序
中山真彰, 井上哲圭, 中山浩次, 大原直也
Journal of Oral Biosciences Supplement (Web) 2013 2013
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歯肉上皮細胞におけるPorphyromonas gingivalis HbRによるIL-8産生
藤田佑貴, 藤田佑貴, 中山真彰, 内藤真理子, 山近英樹, 中山浩次, 大原直也, 飯田征二
日本細菌学雑誌 67 ( 1 ) 2012
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Porphyromonas gingivalis由来タンパク質HbRのIL-8産生誘導解析
中山真彰, 藤田佑貴, 藤田佑貴, 内藤真理子, 中山浩次, 大原直也
トキシンシンポジウム予稿集 59th 2012
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Porphyromonas gingivalisによるAkt脱リン酸化機構とその意義
中山真彰, 藤田佑貴, 井上哲圭, 大原直也
日本細菌学雑誌 67 ( 1 ) 2012
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Porphyromonas gingivalisによるAkt/GSK3betapathwayの制御
中山真彰, 井上哲圭, 大原直也
Journal of Oral Biosciences Supplement (Web) 2012 2012
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国際共同基盤研究に応用する抗酸菌感染症研究の整備 宿主への侵入および宿主内生存に関わる抗酸菌の分子と宿主要因に関する研究
大原直也, 小林和夫, 岡部真裕子, 中山真彰
国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成22年度 総括・分担研究報告書 2011
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H.pylori VacAによるマクロファージ系細胞U937からのIL-8産生機序の解析
久恒順三, 中山真彰, 磯本一, 松島加代子, 河野茂, 倉園久生, 平山壽哉
日本細菌学雑誌 63 ( 1 ) 2008
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ヘリコバクター・ピロリが産生するVacAのアポトーシス誘発機構について
磯本一, 松本章子, 久恒順三, 中山真彰, 河野茂, 平山壽哉
日本細菌学雑誌 63 ( 1 ) 2008
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食道細胞におけるH.pylori空胞化毒素VacAシグナル伝達撹乱作用
松島加代子, 磯本一, 松本章子, 水田陽平, 河野茂, 中山真彰, 久恒順三, 平山壽哉
GI Forefront 3 ( 2 ) 2008
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Helicobacter pyloriの病原性 新たなる発見 Helicobacter pylori VacAに関する最近の研究動向とわれわれの取り組み
平山壽哉, 久恒順三, 中山真彰, 山崎栄樹
Helicobacter Research 12 ( 4 ) 2008
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H.pylori感染胃粘膜におけるCCL20発現の検討
吉田亮, 吉田亮, 磯本一, 松本章子, 松島加代子, 水田陽平, 神田哲郎, 神田哲郎, 河野茂, 林徳眞吉, 久恒順三, 中山真彰, 平山壽哉
日本消化器病学会雑誌 104 2007
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H.pylori空胞化毒素(VacA)の毒性発現機序
中山真彰, 和田昭裕, 和田昭裕, 山崎栄樹, 山崎栄樹, 西義人, 久恒順三, 八尋錦之助, 平山寿哉
日本細菌学雑誌 61 ( 1 ) 2006
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H.pyloriが産生する空胞化毒素VacAのRPTP βのフォスファターゼ活性に与える影響
山崎栄樹, 山崎栄樹, 和田昭裕, 和田昭裕, 中山真彰, 久恒順三, 西義人, 平山寿哉
日本細菌学雑誌 61 ( 1 ) 2006
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H.pyloriの空胞化致死毒素(VacA)の作用機序へのRPTP βの役割
和田昭裕, 和田昭裕, 高橋章, 山崎栄樹, 山崎栄樹, 藤原由似子, 中山真彰, 久恒順三, 西義人, 平山寿哉
日本細菌学雑誌 61 ( 1 ) 2006
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H.pylori VacAはp38及びErk1/2シグナル伝達系を介してCyclooxygenase-2mRNAの発現誘導をこう進する
久恒順三, 中山真彰, 山崎栄樹, 山崎栄樹, 西義人, 和田昭裕, 和田昭裕, 片方陽太郎, 平山寿哉
日本細菌学雑誌 61 ( 1 ) 2006
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H.pyloriの空胞化致死毒素(VacA)の作用機序へのガングリオシドの関与
和田昭裕, 山崎栄樹, 中山真彰, 西義人, 久恒順三, 平山寿哉
日本細菌学雑誌 60 ( 1 ) 2005
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H.pylori VacAのチャネル活性とp38 MAP kinase活性化との関連性について
久恒順三, 中山真彰, 山崎栄樹, 西義人, 和田昭裕, 平山寿哉
日本細菌学雑誌 60 ( 1 ) 2005
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H.pyloriの胃粘膜傷害のメカニズム:どこまで解明されたか-最新の知見-細菌学的サイドからのアプローチ(細菌側病原因子)VacAの構造と毒性発現
平山寿哉, 和田昭裕, 中山真彰, 西義人, 久恒順三
日本臨床 63 2005
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H.pyloriが産生する空胞化致死毒素VacAによるミトコンドリア障害機序の解析
山崎栄樹, 和田昭裕, 中川一路, 船尾純子, 中山真彰, 西義人, 久恒順三, 平山寿哉
日本細菌学雑誌 60 ( 1 ) 2005
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H.pyloriが産生する空胞化毒素VacAのラフトを介した毒性発現機序
中山真彰, 和田昭裕, 山崎栄樹, 西義人, 久恒順三, 八尋錦之助, 平山寿哉
日本細菌学雑誌 60 ( 1 ) 2005
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ヘリコバクター・ピロリ空胞化致死毒素(VacA)のAZ-521細胞に対する細胞致死活性
和田昭裕, 山崎栄樹, 中山真彰, 西義人, 大串賢一, 平山寿哉
日本細菌学雑誌 59 ( 1 ) 2004
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H.pylori VacAの毒性発現における受容体とlipid raftの役割
中山真彰, 和田昭裕, 大串賢一, 西義人, 山崎栄樹, 八尋錦之助, 平山寿哉
日本細菌学雑誌 59 ( 1 ) 2004
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H.pylori空胞化毒素を阻害するヒト血清糖蛋白の同定
西義人, 和田昭裕, 中山真彰, 大串賢一, 山崎栄樹, 河野茂, 平山寿哉
日本細菌学雑誌 59 ( 1 ) 2004
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H.pyloriの空胞化致死毒素(VacA)受容体RPTPβの結合領域解析
八尋錦之助, 和田昭裕, 中山真彰, 平山寿哉, 野田公俊
日本細菌学雑誌 59 ( 1 ) 2004
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Salmonella enteritidis FliCのhuman β-defensin-2発現誘導機序
大串賢一, 和田昭裕, 新留琢郎, 中山真彰, 西義人, 山崎栄樹, 倉園久生, 平山寿哉
日本細菌学雑誌 59 ( 1 ) 2004
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図解Helicobacter pylori技術講座No.38 図解:Helicobacter pylori空胞化毒素(VacA)の毒性測定
平山寿哉, 和田昭裕, 八尋錦之助, 山崎栄樹, 中山真彰, 久恒順三, 西義人
Helicobacter Research 8 ( 5 ) 2004
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G401細胞では受容体型チロシンフォスファターゼalphaがH.pyloriVacA毒素の受容体蛋白である
平山寿哉, 八尋錦之助, 中山真彰, 新留琢郎, 青柳東彦, 和田昭裕
日本細菌学雑誌 58 ( 1 ) 2003
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Studies on the palladium complexes formed by degradation of multidentate ligands.
馬越啓介, 中宮慶子, 中山真彰, 河野博之, 大西正義
日本化学会講演予稿集 79th ( 1 ) 2001
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Synthesis and ligand exchange of palladium(II) and platinum(II) polypyridylamine complexes with uncoordinated pyridyl arm.
井坂忠晴, 中山真彰, 馬越啓介, 大西正義, SOKOLOV M N, 阿部正明, 佐々木陽一
錯体化学討論会講演要旨集 50th 2000
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Presentations
Presentations
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微生物学の基本と感染症の現況
中山真彰
2023年度 岡山大学公開講座「最新歯科医学を学ぶ ~歯科医療従事者対象リカレント教育 2023~（全4回）」 2023.12.7
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Event date： 2023.10.5 - 2023.12.7
Presentation type：Public lecture, seminar, tutorial, course, or other speech
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Porphyromonas gingivalis gingipains induce COX-2 expression and PGE2 production via phospholipase C
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Event date： 2023.3.16 - 2023.3.18
Language：Japanese Presentation type：Poster presentation
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Porphyromonas gingivalis gingipains are significant virulence factors inducing COX-2 expression/PGE2 production in periodontal disease
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Event date： 2023.3.1
Language：Japanese Presentation type：Poster presentation
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葉酸代謝系酵素の発現量が抗結核薬パラアミノサリチル酸に対する感受性に与える影響
中山 真彰, 有村 友紀, 山口 智之, 竜門 亜矢子, 中島 千絵, 鈴木 定彦, 大原 直也
第74回日本細菌学会中国・四国支部総会
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Event date： 2022.10.1
Language：Japanese Presentation type：Oral presentation (general)
Venue：WEB開催（岡山）
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The role of phospholipase on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production
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Event date： 2022.9.17 - 2022.9.19
Language：Japanese Presentation type：Poster presentation
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Lautropia mirabilisの分離・培養および検出法の確立と分離株の薬剤感受性に関する解析
佐藤 あやめ, 中山 真彰, 藤井 伸治, 松岡 賢市, 前田 嘉信, 和田 祟之, 曽我賢彦, 大原 直也
第95回日本細菌学会総会
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Event date： 2022.3.29 - 2022.3.31
Language：Japanese Presentation type：Poster presentation
Venue：WEB（オンライン）開催（東京）
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Porphyromonas gingivalis ジンジパインによるCOX-2発現とPGE2産生におけるカルシウムチャネルの役割
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第95回日本細菌学会総会
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Event date： 2022.3.29 - 2022.3.31
Language：Japanese Presentation type：Poster presentation
Venue：WEB（オンライン）開催（東京）
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The molecular mechanism of Porphyromonas gingivalis gingipains-induced COX-2 expression via the calcium channels
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Event date： 2021.10.9 - 2021.10.17
Language：Japanese Presentation type：Poster presentation
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カルシウムチャネルを介したPorphyromonas gingivalis ジンジパインによるCOX-2発現の分子機序
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第74回日本細菌学会中国・四国支部総会
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Event date： 2021.10.9
Language：Japanese Presentation type：Oral presentation (general)
Venue：WEB開催（広島）
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Porphyromonas gingivalis ジンジパインによるCOX-2発現における細胞外カルシウム流入の重要性
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第94回日本細菌学会総会
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Event date： 2021.3.23 - 2021.3.25
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
Venue：WEB開催（岡山）
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シンポジウム１「At the front-line:Etiology of periodontitis」-The significant role of Porphyromonas gingivalis “Gingipains” as a virulence factor on periodontal inflammation Invited International conference
Masaaki Nakayama
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Event date： 2020.11.7
Language：English Presentation type：Oral presentation (invited, special)
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Involvement of intracellular calcium on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production
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Event date： 2020.9.11 - 2020.10.9
Language：Japanese Presentation type：Poster presentation
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PGN_0296 Operon as a Regulator for Porphyromonas gingivalis Gingipain Secretion. International conference
Shintaro Ono, Masaaki Nakayama, Naoya Ohara, and Shogo Takashiba
2020 IADR/AADR/CADR General Session & Exhibition
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Event date： 2020.3.18 - 2020.3.21
Language：English Presentation type：Poster presentation
Venue：Washington, D.C. USA
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The involvement of calcium inflax on P. gingivalis gingipains-induced COX-2 expression
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Event date： 2020.2.19 - 2020.2.21
Language：Japanese Presentation type：Oral presentation (general)
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P. gingivalis ジンジパインによるCOX-2発現誘導における細胞内Ca2+の関与
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第72回日本細菌学会中国・四国支部総会
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Event date： 2019.11.23 - 2019.11.24
Language：Japanese Presentation type：Oral presentation (general)
Venue：米子市文化ホール イベントホール（鳥取・米子）
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Porphyromonas gingivalisのPGN_0297の機能解析
小野 晋太郎,中山 真彰,高柴 正悟,大原 直也
第62回秋季日本歯周病学会学術大会
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Event date： 2019.10.25 - 2019.10.26
Language：Japanese Presentation type：Poster presentation
Venue：北九州国際会議場および西日本総合展示場（福岡・北九州）
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Analysis of Porphyromonas gingivalis PGN_0296 operon
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Event date： 2019.10.12 - 2019.10.14
Language：Japanese Presentation type：Poster presentation
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Involvement of intracellular calcium on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production
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Event date： 2019.10.12 - 2019.10.14
Language：Japanese Presentation type：Poster presentation
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pYTプラスミドの非結核性抗酸菌における応用の可能性の検討
野崎 高儀, 中山 真彰, 大原 直也, 吉田 志緒美, 阿戸 学
第94回⽇本結核病学会総会
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Event date： 2019.6.7 - 2019.6.8
Language：Japanese Presentation type：Oral presentation (general)
Venue：iichiko総合文化センター、ホテル日航大分 オアシスタワー（大分）
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非結核性抗酸菌におけるpYT系プラスミド利用の可能性（The possibility of the pYT plasmid in the use of geneticanalysis of NTM）
野崎高儀,中山真彰,小川みどり,吉田志緒美,阿戸学,大原直也
第92回日本細菌学会総会
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Event date： 2019.4.23 - 2019.4.25
Language：Japanese Presentation type：Poster presentation
Venue：札幌コンベンションセンター（北海道・札幌）
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Analysis of a rapid growing Mycobacterium avium subspecieshominissuis 104 strain
河喜多智美,吉田光範,鈴木仁人,中田登,瀧井猛将,中山真彰,梁明秀,星野仁彦,阿戸学,大原直也
第92回日本細菌学会総会
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Event date： 2019.4.23 - 2019.4.25
Language：Japanese Presentation type：Poster presentation
Venue：札幌コンベンションセンター（北海道・札幌）
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P. gingivalis ジンジパインによるCOX-2発現における細胞内Ca2+の役割
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第92回日本細菌学会総会
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Event date： 2019.4.23 - 2019.4.25
Language：Japanese Presentation type：Poster presentation
Venue：札幌コンベンションセンター（北海道・札幌）
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Porphyromonas gingivalis ジンジパインのCOX-2発現/PGE2産生の分子機序
中山 真彰
第71回歯日本細菌学会関西支部総会
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Event date： 2018.10.28
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
Venue：大阪大学中之島センター佐治敬三メモリアルホール（10階）（大阪）
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P. gingivalis ジンジパインによるCOX-2発現とPGE2産生における細胞内Ca2+の重要性
中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
第71回歯日本細菌学会中国四国支部総会
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Event date： 2018.10.6 - 2018.10.7
Language：Japanese Presentation type：Oral presentation (general)
Venue：愛媛大学 城北キャンパス グリーンホール
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The role of PGN_0301 gene on Porphyromonas gingivalis
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Porphyromonas gingivalis gingipains induce COX-2 expression and PGE2 production via activation of MEK/ERK/AP-1 and IKK/NF-kBp65
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Investigation of genes involved in promoting the growth rate of BCG
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Event date： 2018.3.27 - 2018.3.29
Language：Japanese Presentation type：Poster presentation
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Inhibitory mechanism of Rv3406 expression by Rv3405c in BCG Tokyo
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Event date： 2018.3.27 - 2018.3.29
Language：Japanese Presentation type：Poster presentation
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Molecular mechanism of COX-2 expression and PGE2 production by Porphyromonas gingivalis gingipains
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Event date： 2018.3.27 - 2018.3.29
Language：Japanese Presentation type：Poster presentation
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Inhibitory mechanism of JTY3476 expression by JTY3475 in BCG Tokyo International conference
The 52nd US-Japan Mycobacteria Panel Meeting 2018 in Niigata, Japan
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Functions of the virulence factor from periodontal pathogens on periodontal diseases Invited International conference
Masaaki Nakayama
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Event date： 2017.11.17 - 2017.11.19
Language：English Presentation type：Oral presentation (invited, special)
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P. gingivalis ジンジパインによるCOX-2発現およびPGE2産生の分子解析
中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
第70回歯日本細菌学会中国四国支部総会
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Event date： 2017.10.14 - 2017.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：広島大学 東広島キャンパス 学士会館 2階 レセプションホール
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B C G に存在する転写抑制因子R v 3 4 0 5 c の解析
白崎 かおり, 中山 真彰, ○橘 理人, 山本 三郎,瀧井 猛将, 岡部 真裕子, 阿戸 学, 竜門 亜矢子, 小崎 弘貴, 上岡 寛, 大原 直也
第70回歯日本細菌学会中国四国支部総会
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Event date： 2017.10.14 - 2017.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：広島大学 東広島キャンパス 学士会館 2階 レセプションホール
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非結核性抗酸菌（ n o n - t u b e r c u l o u s m y c o b a c t e r i a ， N T M ） の薬剤排出能 に関する検討
小崎 弘貴,中山 真彰,橘 理人,西内 由紀子,阿戸 学,大原 直也
第70回歯日本細菌学会中国四国支部総会
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Event date： 2017.10.14 - 2017.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：広島大学 東広島キャンパス 学士会館 2階 レセプションホール
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BCG ThyA，ThyX変異株の解析
竜門亜矢子,中山真彰,橘理人,小崎弘貴,大原直也
第59回歯科基礎医学会学術大会
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Event date： 2017.9.16 - 2017.9.18
Language：Japanese Presentation type：Oral presentation (general)
Venue：松本歯科大学キャンパス
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非結核性抗酸菌（non-tuberculous mycobacteria，NTM）の薬剤排出能に関する検討
小崎弘貴,中山真彰,橘理人,大原直也
第59回歯科基礎医学会学術大会
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Event date： 2017.9.16 - 2017.9.18
Language：Japanese Presentation type：Oral presentation (general)
Venue：松本歯科大学キャンパス
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Porphyromonas gingivalis gingipains induce PGE2 production via COX-2 expression
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Event date： 2017.9.16 - 2017.9.18
Language：Japanese Presentation type：Oral presentation (general)
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Porphyromonas gingivalis gingipains disturb Akt signaling pathway via inactivation of PI3K International conference
Masaaki Nakayama, Mariko Naito, Koji Nakayama, Naoya Ohara
IUMS 2017: International Union of Microbiological Societies
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Event date： 2017.7.17 - 2017.7.21
Language：English Presentation type：Poster presentation
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Porphyromonas gingivalis gingipains induce PGE2 production via COX-2 expression by activation of MEK1/2 and NF-kB International conference
Masaaki Nakayama, Mariko Naito, Koji Nakayama, Naoya Ohara
PgMelbourne2017: The 3rd International Conference on Porphyromonas gingivalis and Related Species in Oral and Systemic Diseases
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Event date： 2017.5.14 - 2017.5.16
Language：English Presentation type：Oral presentation (general)
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Mycobacterium aviumの酸性環境下でのアルギニンデイミナーゼの活性化機構の解析
小川翔大, 山本龍二, 堀田康弘, 中山 真彰, 大原直也, 瀧井猛将
第87回実験結核研究会
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Event date： 2017.3.22
Language：Japanese Presentation type：Oral presentation (general)
Venue：東京
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BCG Tokyo 172-1に存在するサブポピュレーションI型とII型に関する新たな知見
田村 庄平, 白崎 かおり, 中山 真彰, 藤原 永年, 和田 崇之, 瀧井 猛将, 山本 三郎, 岡部 真裕子, 阿戸 学, 小崎 弘貴, 竜門 亜矢子, 大原 直也
第87回実験結核研究会
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Event date： 2017.3.22
Language：Japanese Presentation type：Oral presentation (general)
Venue：東京
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BCG Tokyo RD16 領域に存在する JTY_3475c は JTY_3476 の遺伝子発現を負に制御する
白崎 かおり, 中山 真彰, 山本 三郎, 瀧井 猛将, 岡部 真裕子, 阿戸 学, 上岡 寛, 大原 直也
第90回日本細菌学会総会
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Event date： 2017.3.19 - 2017.3.21
Language：Japanese Presentation type：Poster presentation
Venue：仙台国際センター展示棟（宮城）
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The significance of P. gingivalis gingipains on Periodontal diseases
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Event date： 2017.3.19 - 2017.3.21
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
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Porphyromonas gingivalis gingipains cause cyclooxygenase 2 expression and prostaglandin E2 production
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Event date： 2017.3.19 - 2017.3.21
Language：Japanese Presentation type：Poster presentation
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Involvement of BCG cell wall glycolipid PDIM / PGL in resistance to bile acids
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Event date： 2017.3.19 - 2017.3.21
Language：Japanese Presentation type：Poster presentation
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P. gingivalis ジンジパインの宿主細胞応答を介した病原性機能解析 Invited
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第69回日本細菌学会中国・四国支部総会
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Event date： 2016.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：かがわ国際会議場（香川）
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チミジル酸合成酵素 ThyX の過剰発現は BCG の増殖を促進させる
竜門 亜矢子, 中山 真彰, 有村 友紀, 阿戸 学, 中島 千絵, 鈴木 定彦, 小崎 弘貴, 大原 直也
第69回日本細菌学会中国・四国支部総会
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Event date： 2016.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：かがわ国際会議場（香川）
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BCG の細胞壁糖脂質 PDIM/PGL の胆汁酸に対する抵抗性への関与
田村 庄平, 中山 真彰, 藤原 永年, 和田 崇之, 山本 三郎, 小崎 弘貴, 大原 直也
第69回日本細菌学会中国・四国支部総会
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Event date： 2016.10.15
Language：Japanese Presentation type：Oral presentation (general)
Venue：かがわ国際会議場（香川）
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Role of Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp on the PI3 kinase/Akt signaling pathway
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Event date： 2016.8.24 - 2016.8.26
Language：English Presentation type：Poster presentation
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Molecular mechanism of attenuation of the PI3 kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp Invited
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Event date： 2016.8.24 - 2016.8.26
Language：Japanese Presentation type：Oral presentation (invited, special)
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P. gingivalis ジンジパインによるPI3K/Akt経路撹乱の分子解析
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第89回日本細菌学会総会
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Event date： 2016.3.23 - 2016.3.25
Language：Japanese Presentation type：Poster presentation
Venue：大阪国際交流センター（大阪）
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抗酸菌のPAS耐性機序の解明：BCG thyX欠損株および過剰発現株の作製
有村 友紀, 中山 真彰, 妹尾 昌紀, 田川 淳平, 阿戸 学, 中島 千絵, 鈴木 定彦, 中山 浩次, 小林 和夫, 大原 直也
第89回日本細菌学会総会
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Event date： 2016.3.23 - 2016.3.25
Language：Japanese Presentation type：Poster presentation
Venue：大阪国際交流センター（大阪）
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BCG thyX変異株の作製とその性状解析
有村 友紀, 中山 真彰, 妹尾 昌紀, 田川 淳平, 阿戸 学, 中島 千絵, 鈴木 定彦, 中山 浩次, 大原 直也
第68回日本細菌学会中国・四国支部総会
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Event date： 2015.10.3 - 2015.10.4
Language：Japanese Presentation type：Oral presentation (general)
Venue：岡山大学鹿田キャンパス 地域医療人育成センターおかやま (MUSCAT CUBE)（岡山）
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P. gingivalis ジンジパインによるPI3K/Akt経路撹乱の分子解析
中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第68回日本細菌学会中国・四国支部総会
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Event date： 2015.10.3 - 2015.10.4
Language：Japanese Presentation type：Oral presentation (general)
Venue：岡山大学鹿田キャンパス 地域医療人育成センターおかやま (MUSCAT CUBE)（岡山）
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BCGにおけるcyclic-di-GMP菌体内過剰発現の影響
妹尾 昌紀, 中山 真彰, 有村 友紀, 大原 直也
第68回日本細菌学会中国・四国支部総会
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Event date： 2015.10.3 - 2015.10.4
Language：Japanese Presentation type：Oral presentation (general)
Venue：岡山大学鹿田キャンパス 地域医療人育成センターおかやま (MUSCAT CUBE)（岡山）
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Porphyromonas gingivalisにおけるsigma-54の機能
加野 小奈美, 井上 哲圭, 中山 真彰, 内藤 真理子, 田川 淳平, 中山 浩次, 上岡 寛, 大原 直也
第68回日本細菌学会中国・四国支部総会
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Event date： 2015.10.3 - 2015.10.4
Language：Japanese Presentation type：Oral presentation (general)
Venue：岡山大学鹿田キャンパス 地域医療人育成センターおかやま (MUSCAT CUBE)（岡山）
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Attenuation of the PI3 kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp
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Event date： 2015.9.11 - 2015.9.13
Language：English Presentation type：Poster presentation
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A single base insertion in 16S rRNA gene confers Streptomycin dependence in Mycobacterium bovis BCG
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Event date： 2015.3.26 - 2015.3.28
Language：Japanese Presentation type：Poster presentation
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歯周病原細菌の感染による免疫応答と破骨細胞分化制御の相関性
中山 真彰, 中山 浩次, 大原 直也
第88回日本細菌学会総会
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Event date： 2015.3.26 - 2015.3.28
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
Venue：長良川国際会議場（岐阜）
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Porphyromonas gingivalisの表層蛋白質の修飾と機能に関与する分子の解析
田口 裕子, 佐藤 啓子, 雪竹 英治, 井上 哲圭, 中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第88回日本細菌学会総会
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Event date： 2015.3.26 - 2015.3.28
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
Venue：長良川国際会議場（岐阜）
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Porphyromonas gingivalis ATCC33277株rpoN低発現株の性状解析
加野 小奈美, 井上 哲圭, 田口 裕子, 田川 淳平, 中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
第88回日本細菌学会総会
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Event date： 2015.3.26 - 2015.3.28
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
Venue：長良川国際会議場（岐阜）
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細菌感染による破骨細胞分化への自然免疫応答の重要性
中山 真彰, 中山 浩次, 大原 直也
第88回日本細菌学会総会
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Event date： 2015.3.26 - 2015.3.28
Language：Japanese Presentation type：Poster presentation
Venue：長良川国際会議場（岐阜）
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A new aspect of Porphyromonas gingivalis infection; Gingipains disturb the host cell PI3K/Akt signaling pathway Invited
Masaaki Nakayama
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Event date： 2015.2.5
Language：English Presentation type：Oral presentation (invited, special)
Awards
Awards
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平成28年度(第28回)歯科基礎医学会学術奨励賞
2016 歯科基礎医学会
中山 真彰
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平成28年度(第69回)日本細菌学学会中国・四国支部総会若手研究者奨励賞
2016 日本細菌学学会中国・四国支部総会
中山 真彰
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平成25年度第35回研究助成金
2013 公益財団法人両備檉園記念財団 歯周病原細菌によるPI3K/Akt経路抑制機構の解明と感染における生理的意義
中山 真彰
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Research Projects
Research Projects
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The study of novel targets for infertility, with a focus on the link between oral disease (periodontal disease) and the uterus.
Grant number：24K22249 2024.06 - 2027.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
大森 一弘, 中山 真彰, 大原 利章, 萬代 大樹
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歯周病細菌主要病原因子ジンジパインの宿主直接作用と必須新奇オペロンの解明
Grant number：24K02614 2024.04 - 2028.03
日本学術振興会 科学研究費助成事業 基盤研究(B)
大原 直也, 中山 真彰, 大森 一弘, 佐藤 啓子, 大原 直子, 武部 克希
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A Novel Mechanism of Infertility through the Oral-Uterine Interaction Induced by Periodontal Infection and Inflammation
Grant number：23K27773 2024.04 - 2027.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
大森 一弘, 中山 真彰, 大原 利章, 萬代 大樹
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A Novel Mechanism of Infertility through the Oral-Uterine Interaction Induced by Periodontal Infection and Inflammation
Grant number：23H03083 2023.04 - 2027.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
大森 一弘, 中山 真彰, 大原 利章, 萬代 大樹
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結核菌群におけるメチオニン合成代謝系酵素の役割と抗結核薬ターゲットの検討
2023.04 - 2024.03
北海道大学 2023年度北海道大学人獣共通感染症国際共同研究所一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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結核菌群における葉酸代謝系酵素の機能解析および抗結核薬ターゲットの可能性追求
2022.06 - 2023.03
北海道大学 2022年度北海道大学人獣共通感染症国際共同研究所一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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新興病原体エリザベスキンギア菌によるマクロファージ成熟抑制現象の解明
Grant number：22K07069 2022.04 - 2026.03
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)
後藤 和義, 横田 憲治, 中山 真彰
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抗結核薬創出を目指した葉酸代謝系の新規代謝酵素の探索・同定と機能解析
2021.05 - 2022.03
北海道大学 2021年度北海道大学人獣共通感染症リサーチセンター一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\250000
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Molecular mechanism of host cell response disruption and periodontal tissue destruction by proteases produced by periodontal bacteria
Grant number：21K09842 2021.04 - 2026.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
中山 真彰, 大森 一弘, 大原 直也
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Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）
本研究の目的は，「歯周病原細菌と宿主細胞間で起こる感染現象の分子基盤を細胞・分子生物学的アプローチにより構築し，歯周病菌が産生する病原性プロテ アーゼの機能解析を行ない、歯周病の発症機序を解明する」ことである。本申請研究では歯周病細菌の感染による歯周病発症と病態形成機序を解明するために、 歯周病細菌Porphyromonas gingivalis (P. gingivalis)が産生する病原因子であるプロテアーゼ「ジンジパイン」に着目し、宿主細胞の主要なシグナル伝達経路 の撹乱機構を中心に分子解析を行なう。これまでの研究では、歯周病の発症におけるジンジパインの役割を調べるために、ジンジパイン完全欠損株とその野生株 を用いた感染実験による比較解析を行ない、歯周組織の炎症で発現がみられるCOX-2やPGE2の産生について調べた。P. gingivalisのLPSや線毛がCOX-2発現や PGE2産生に関与することは知られていたが、ジンジパインが発現誘導に関わる因子であることは報告がなかった。我々の結果から、本菌が産生するジンジパイン はLPSや線毛よりも強くCOX-2発現やPGE2産生を誘導することを明らかにした。またジンジパインによるCOX-2発現の分子機序について宿主細胞応答を調べたとこ ろ、ERKとIKKの2つのシグナル伝達経路の活性化とそれぞれ転写因子c-Jun/c-FosとNF-kBp65の活性化が重要であることを示し、さらには細胞内カルシウムの重要性も明らかにした。今後は、COX-2発現と PGE2産生 に繋がる上流因子の分子解析を行ない、ジンジパインが作用する細胞膜上の入り口となる因子の解析を行なう。
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抗結核薬創出のためのメチオニン合成代謝系の理解と新規代謝酵素の探索・同定
2020.05 - 2021.03
北海道大学 2020年度北海道大学人獣共通感染症リサーチセンター一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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新規抗結核薬の開発を目指した葉酸代謝系に関与する代謝酵素の役割
2019.05 - 2020.03
北海道大学 2019年度北海道大学人獣共通感染症リサーチセンター一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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超高齢社会での応用を目指す低分子化合物terreinの標的分子の同定・機能解析
Grant number：19K10108 2019.04 - 2022.03
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)
大森 一弘, 中山 真彰, 竹内 恒, 高柴 正悟, 萬代 大樹
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Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
超高齢社会を迎えた我が国において，食生活を司る口腔機能を維持することは健康寿命を延伸する上で必須である。一方，8020達成率が50%を超えた現代において，高齢者の口腔内に存在する歯自体が感染源となり，口腔疾患の罹患率が上昇する新たな問題が生じている。 そのため，安全・簡便に応用できる新規口腔治療法の開発が社会的に望まれる。申請者らの研究グループは，抗菌・抗炎症作用を有する一方，極めて細胞毒性が低い真菌由来代謝産物terreinに着目し，1) 有機化学的大量合成経路の確立，2)抗IL-6効果，3)破骨細胞分化抑制効果等を報告した。しかし，terreinの作用機序(標的分子)は未だ不明であり，terreinの有益性を検証する上で標的分子の同定は必要不可欠である。本研究では，様々な薬理作用を期待できる低分子化合物terreinの標的分子を同定し，歯内・歯周疾患モデルを用いた機能解析を行い，terreinの新たな口腔治療薬（治療法）としての可能性を検証することを目的としている。本年度は，terreinの破骨細胞分化抑制メカニズムの一端として、RANKL誘導性のNFATc1の発現を抑制するメカニズムの一端を解明し，報告した。従来考えていたRANKL刺激時に誘導されるNF-kaB経路、MAPKs経路に影響を与えず、別の経路を抑制することによって骨吸収を抑制する可能性が示唆された。今後，terreinの標的分子を同定していく上で，その候補分子の数を絞り込む上で有用な結果が得られたと判断する。
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抗酸菌の葉酸代謝機構の解明と新規抗結核薬の開発に関する研究
2018.06 - 2019.03
北海道大学 平成30年度北海道大学人獣共通感染症リサーチセンター一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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The mechanism of periodontal tissue destruction by proteases from periodontal bacteria Porpyromonas gingivalis.
Grant number：17K11668 2017.04 - 2021.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Nakayama Masaaki
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Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）
The purpose of this study is to reveal the molecular mechanism of infection between periodontal pathogenic bacteria and host cells using cellular and molecular biological approaches, and to analyze the function of pathogenic proteases produced by periodontal pathogenic bacteria to clarify the pathogenesis of periodontal disease. In this study, we focused on gingipains, which are cysteine proteases, produced by Porphyromonas gingivalis (P. gingivalis), to elucidate the pathogenesis of periodontal disease infected with P. gingivalis. We examined the host cell response to the molecular mechanism of COX-2 expression by gingipains and showed that activation of two signaling pathways, ERK and IKK, and found that intracellular calcium is required for COX-2 expression and PGE2 production as the upstream factors.
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Understanding the pathogenicity of periodontal disease onset and systemic disease exacerbation caused by periodontal bacteria
Grant number：17H04378 2017.04 - 2021.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
OHARA Naoya
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Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）
In this study, we focused on the proteases "gingipains", which is one of the virulence factors produced by the periodontal pathogen Porphyromonas gingivalis. We studied the molecular mechanism of COX-2 expression and PGE2 production induced by gingipains on P. gingivalis-infected monocyte/macrophage cells. In these events, we found the activation of ERK1/2 and IKK, activation of transcription factors AP-1 (c-Jun/c-Fos) and NF-κBp65. Furthermore, we clarified that gingipains-induced COX-2 expression and PGE2 production required the increase in calcium ion concentration due to intracellular influx from outside the cells.
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遅発育性抗酸菌の増殖速度を規定する因子の解析
2017.04 - 2018.03
北海道大学 平成２９年度北海道大学人獣共通感染症リサーチセンター一般共同研究
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\300000
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Grant number：16K11549 2016.04 - 2019.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Omori Kazuhiro
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Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）
In this study, we examined the possibility of the anti-inflammatory small molecule compound terrein as a therapeutic agent for inflammatory bone resorption diseases (especially endodontic or periodontal diseases). As a result of present study, (1) success of synthesized new terrein analogues, which have inhibitory effect of osteoclast differentiation, (2) one of the intracellular target molecules of terrain is JAK1, (3) intraperitoneal administration of terrein significantly inhibited alveolar bone resorption in the mouse ligature-induced periodontal disease model, and terrain suppressed the infiltration of inflammatory cells into the subepithelial region. The results suggest that terrein, a low molecular weight compound, may be applied as a treatment for endodontic or periodontal diseases.
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Analysis the virulence of Mycobacterium tuberculosis based of rapid-growing BCG
Grant number：16K15277 2016.04 - 2018.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
Ohara Naoya, KOSAKI Hirotaka, RYUMON Ayako
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Grant amount：\3510000 （ Direct expense: \2700000 、 Indirect expense：\810000 ）
Mycobacterium tuberculosis is an intracellular pathogen, has a remarkably slow growth rate, and survives long periods of time in the host. We found that overexpression of thyX in BCG (pthyX) resulted in accelerating its growth rate. We analyzed the gene expression profiles in pthyX using RNAseq. Several genes in folate metabolism pathway were up-ragulated in pthyX. We concluded that tetrahydrofolate is the key molecule in the control of the growth rate of slow-growing mycobacteria.
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Effect of IL-22 on immune response against periodontal bacteria
Grant number：26463151 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Kato-kogoe Nahoko
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Grant amount：\4940000 （ Direct expense: \3800000 、 Indirect expense：\1140000 ）
This study focused on the effects of IL-22 on the response against periodontal bacteria in gingival epithelial cells. We found that IL-22 reduced gingival epithelial cell differentiation and subsequently decreased antibiotic peptide productivity. In addition, incubation with IL-22 decreased the invasion of Porphyromonas gingivalis into the gingival epithelial cells. The results suggest that IL-22 augments resistance to bacterial invasion of gingival epithelial cells.
The effect of IL-22 on immune response against periodontal bacteria. -
The role of gingipains from P. gingivalis on host cell responses
Grant number：26861573 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
Nakayama Masaaki
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Grant amount：\3770000 （ Direct expense: \2900000 、 Indirect expense：\870000 ）
Peridontal diseases are chronic oral bacterial infectious diseases which indicate inflammation of periodontal tissues, alveolar bone loss, and, leading to loss of tooth. In this research, Porphyromonas gingivalis, which is one of the most major oral pathogens, produces cysteine proteases called as gingipains. The gingipains attenuate PI3 kinase/Akt signaling pathway, and Akt downstream proteins, which are mTOR, GSK3, Bad, PRAS40, and MDM2, are also altered the their level of phosphorylation by gingipains in gingival epithelial cells. Taken together, their activity is disturbed by gingipains in parallel with inactivation of PI3K/Akt.
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Grant number：26293401 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
OHARA Naoya, TAGUCHI Yuko, KANO Konami
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Grant amount：\16510000 （ Direct expense: \12700000 、 Indirect expense：\3810000 ）
Periodontal diseases are chronic oral bacterial infectious diseases. In our study, Porphyromonas gingivalis, which is one of major oral pathogens, produces cysteine proteases called as gingipains. Gingipains attenuate PI3K/Akt signaling pathway, and which is associated with their protease activity from extracellular interaction without invasion of this organisms. Moreover, several downstream proteins of Akt, which are GSK3, mTOR, Bad, PRAS40, and MDM2, are also changed the their phosphorylation level by gingipains in gingival epithelial cells. On the basis of the results, their physiological activity might be dysregulated by gingipains in parallel with inactivation of PI3K/Akt in the cells.
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プロテオーム解析法を用いた未分化能を有する歯肉上皮系前駆細胞における歯周病菌産生毒素の標的膜タンパク質の探索
2014.04 - 2016.03
公益財団法人発酵研究所 2014年度 公益財団法人発酵研究所一般研究助成
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\3000000
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歯周病原細菌によるPI3K/Akt経路抑制機構の解明と感染における生理的意義
2013.10 - 2014
公益財団法人 両備檉園記念財団 平成25年度 第35回両備檉園記念財団研究助成金
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\350000
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PI3K/Akt経路を抑制する歯周病菌産生毒素ジンジパインの病原発現機構と生理的意義の解明
2013.07 - 2016.03
公益財団法人 武田科学振興財団 2013年度武田科学医学系研究奨励
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\2000000
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ＴｒａＳＨ法による歯周病原細菌の宿主細胞内防御系からの回避機構の解明
Grant number：24592765 2012.04 - 2015.03
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)
井上 哲圭, 中山 真彰, 大原 直也
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Grant amount：\5330000 （ Direct expense: \4100000 、 Indirect expense：\1230000 ）
Porphyromonas gingivais (Pg) ATCC 33277株のトランスポゾン変異株ライブラリーのスクリーニングによって新たに見出された本菌の宿主細胞内感染に関わるx遺伝子に関して、本年度の研究により、x遺伝子は本菌の主たる病原因子であるプロテアーゼ（ジンジパイン）の分泌に関わることが明らかとなった。すなわち、新規にx遺伝子の遺伝子欠損株を作製し、血液寒天培地上で培養すると、親株では菌体外に分泌されたジンジパインの作用により黒色集落が形成されるのに対し、x遺伝子欠損株では菌体外ジンジパイン欠損株の特徴である白色集落が形成された。そこで、親株、x遺伝子欠損株およびそのx遺伝子相補株の菌体外ジンジパイン活性の測定を行った。本菌は2種のArg-ジンジパインと1種のLys-ジンジパインを産生する。上記3株の全菌体および培養上清を調製し、各々のジンジパインに特異的な蛍光基質を用いて活性測定を行った。その結果、x遺伝子産物は、3種のジンジパインのいずれの分泌にも関与していることが判明した（第56回歯科基礎医学会にて発表）。さらに、ATCC 33277株のゲノム上にはx遺伝子のorthologが2個存在することもわかった（x2, x3遺伝子）。これらの遺伝子はPgの他の菌株はもとより、近縁のBacteroides属菌種を含む様々な菌種、さらに腸内細菌においてもhomologが広く存在することがわかってきた。このことは、細菌細胞におけるこのx遺伝子の普遍的な機能を示唆しているとも考えられるが、例えば大腸菌においては、菌体外物質の分泌とは異なる機能を有することが報告されており、Pgにおけるx遺伝子産物の役割はマルチファンクショナルなものである可能性も考えられた。今後、Pgにおけるx遺伝子の病原性における役割を検討し、本菌の病原メカニズムの全貌の解明に貢献していく。
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The role of hemoglobin receptor protein from Porphyromonas gingivalis on periodontitis
Grant number：24791999 2012.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
NAKAYAMA Masaaki
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Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）
In this study, we attempted to clarify about the function of hemoglobin receptor (HbR) protein from Porphyromonas gingivalis on the host epithelial cells and the relationship with inflammation in the periodontal diseases. Using gingival epithelial cell line Ca9-22 and primary gingivali epithelial cells, HbR protein induce interleukin-8 within at least 3 h after stimulation. Moreover, we revealed the molecular mechanisms by which HbR protein induced IL-8 production through the activation of p38/CREB and Erk1/2/ATF-2, NF-kB Therefore, these results led us to the possibility that HbR protein is associated with periodontitis by innate immun responses.
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Helicobacter pylori によるp53が制御するアクチン骨格系へ与える影響
2011.10 - 2013.03
浜崎癌研究助成 浜崎癌研究助成
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\500000
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歯周病原細菌Porphyromonas gingivalisによる破骨細胞の分化制御と骨破壊の分子基盤
2010.04 - 2012.03
岡山大学 岡山大学若手研究者スタートアップ研究支援事業
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Authorship：Principal investigator Grant type：Competitive
Grant amount：\800000
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Grant number：22390342 2010 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
OHARA Naoya, NAKAYAMA Masaaki, OHARA Naoko
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Grant amount：\19500000 （ Direct expense: \15000000 、 Indirect expense：\4500000 ）
Porphyromonas gingivalisis the major periodontal pathogens. 1) We identified P. gingivalis genes required for survival in the host cells using newly constructed transposon mutagenesis library of P. gingivalis. 2) We found the novel cellular events in host epithelial cells by challenging of P. gingivalis. Akt and its substrates were dephosphorylated by P. gingivalis infection. These results indicated that P. gingivalis-infection may affect cellular functions including apoptosis, glucose metabolism and cell development in host cells by inactivating the PI3K/AKt pathway.
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Inhibition of RANK ligand-induced osteoclast differentiation by Porphyromonas gingivalis
Grant number：22890115 2010 - 2011
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up Grant-in-Aid for Research Activity Start-up
NAKAYAMA Masaaki
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Grant amount：\2977000 （ Direct expense: \2290000 、 Indirect expense：\687000 ）
In this study, we demonstrated whether P. gingivalis affects osteoclastogenesis induced by RANK/RANKL signaling. Osteoclastic precursor cells were challenged by P. gingivalis with RANKL at the same time, analyzed its differentiation for matured osteoclasts. Interestingly, the osteoclastic precursors were inhibited RANK/RANKL-induced osteoclastogenesis by infection of P. gingivalis. It was, however, contratory to my expectation that osteoclasts were promoted to form the large number of matured cells and activated bone resorption by P. gingivalis infection. According to investigate this inhibition by using precursor cells from knockout mice of TLRs and adaptor factors, MyD88 and TRIF, it revealed that innate immune response through TLR2/MyD88 signaling pathway were related with this inhibition.
Other research activities
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真菌代謝産物Terreinの生理活性物質としての機能解析
2020.04More details
岡山大学・群馬大学 ・岐阜医療科学大学
真菌代謝産物Terreinの破骨細胞分化抑制とメカニズム解明に関わる実験 -
日本医療研究開発機構(AMED)橋渡し研究支援拠点：がん化学療法に伴う口腔粘膜炎の疼痛緩和・発症制御を目指す新規口腔粘膜保護材の開発
2020.04-2022.03More details
研究協力者：抗菌性口腔粘膜保護材開発に向けた口腔内細菌の培養・取り扱いなどのアドバイス
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真菌代謝産物Terreinの生理活性物質としての機能解析
2019.04-2020.03More details
岡山大学・群馬大学 ・岐阜医療科学大学・産業技術総合研究所
真菌代謝産物Terreinの破骨細胞分化抑制とメカニズム解明に関わる実験 -
日本医療研究開発機構(AMED)新興・再興感染症に対する革新的医薬品等開発推進研究事業：結核の発病予測向上と治療期間短縮を目指した生物学的要因の探索
2019-2022.03More details
研究協力者：細菌培養・組み換え・解析、書類作成、会議発表など実質的な分担研究者相当として全般に従事。
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結核菌の葉酸代謝機構の解明と新規抗結核薬の開発に関する研究
2017More details
Department of Microbiology and Immunology,
University Minnesota Medical School
ミネソタ大学医学部微生物免疫学研究室
スーパーグローバル大学創成支援（ＳＧＵ）を通じて、ミネソタ大学医学部のA. Baughn博士と藤田医科大学の港博士と共同研究を行なっている。 -
真菌代謝産物Terreinの生理活性物質としての機能解析
2017-2019.03More details
岡山大学・群馬大学との共同研究
真菌代謝産物Terreinの破骨細胞分化抑制とメカニズム解明に関わる実験 -
歯周病細菌が産生するプロテアーゼの宿主細胞に対する病原発現機序に関わる研究
2011More details
"長崎大学大学院医歯薬学総合研究科口腔病原微生物学分野
（中山浩次博士・内藤真理子博士）"
歯周病細菌が産生するプロテアーゼの宿主細胞に対する病原発現機序に関わる研究について、細菌培養・細菌変異株の作製・細菌学的解析・生化学的実験の面から共同研究を継続している。
Class subject in charge
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Social Activities
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高大連携ーR3高校生のための大学講座
Role(s)：Lecturer
岡山大学 高大連携ーR3高校生のための大学講座 2021.11.20