研究者詳細 - 宮原　信明

論文 - 宮原　信明

分割表示 179 件中 61 - 80 件目／全件表示 >>

Effect of a retinoid X receptor partial agonist on airway inflammation and hyperresponsiveness in a murine model of asthma 査読

Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Naohiro Oda, Daisuke Morichika, Etsuko Murakami, Hikari Nakayama, Koichi Waseda, Mikio Kataoka, Hiroki Kakuta, Mitsune Tanimoto, Arihiko Kanehiro

RESPIRATORY RESEARCH 18 2017年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Background: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners-e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined. The goal of this study is to elucidate the role of RXRs in asthma pathogenesis and the potency of RXR partial agonist in the treatment of allergic airway inflammation and airway hyperresponsiveness using a murine model of asthma.
Methods: We investigated the effect of a novel RXR partial agonist (NEt-4IB) on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in a murine model of asthma. Balb/c mice were sensitized (days 0 and 14) and challenged (days 28-30) with ovalbumin (OVA), and airway inflammation and airway responses were monitored 48 h after the last OVA challenge. NEt-4IB was administered orally on days 25 to 32.
Results: Oral administration of NEt-4IB significantly suppressed AHR and inflammatory cell accumulation in the airways and attenuated the levels of TNF-a in the lung and IL-5, IL-13 and NO levels in bronchoalveolar lavage (BAL) fluid and the number of periodic acid Schiff (PAS)-positive goblet cells in lung tissue. Treatment with NEt-4IB also significantly suppressed NF-.B expression.
Conclusion: These data suggest that RXRs may be of crucial importance in the mechanism of allergic asthma and that the novel RXR partial agonist NEt-4IB may be a promising candidate for the treatment of allergic airway inflammation and airway hyperresponsiveness in a model of allergic asthma.

DOI： 10.1186/s12931-017-0507-z

Pneumocystis Pneumonia Concomitant with Ectopic ACTH Syndrome Caused by a Large Cell Neuroendocrine Carcinoma of the Thymus 査読

Naohiro Oda, Nobuaki Miyahara, Masahiro Tabata, Daisuke Minami, Kiichiro Ninomiya, Arihiko Kanehiro, Motoshi Komatsubara, Kenichi Inagaki, Mitsune Tanimoto, Katsuyuki Kiura

INTERNAL MEDICINE 56 ( 5 ) 551 - 555 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.

DOI： 10.2169/internalmedicine.56.7655

Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease 査読

Naohiro Oda, Nobuaki Miyahara, Hirohisa Ichikawa, Yasushi Tanimoto, Kazuhiro Kajimoto, Makoto Sakugawa, Haruyuki Kawai, Akihiko Taniguchi, Daisuke Morichika, Mitsune Tanimoto, Arihiko Kanehiro, Katsuyuki Kiura

INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 12 1119 - 1124 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：DOVE MEDICAL PRESS LTD

Background: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD) is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated.
Patients and methods: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1) was assessed.
Results: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0 +/- 8.2 years); 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD) stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC), FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8 +/- 1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6 +/- 93.5 mL/year vs -4.7 +/- 118.9 mL/year, P=0.671). After controlling for relevant confounders in multivariate analyses, it was found that beta-blocker use was not significantly associated with the annual decline in FEV1 (beta=-0.019; 95% confidence interval: -0.073 to 0.036; P=0.503).
Conclusion: Long-term beta-blocker use in Japanese COPD patients might not affect the FEV1, one of the most important parameters of lung function in COPD patients.

DOI： 10.2147/COPD.S133071

Safety And Discomfort During Bronchoscopy Performed Under Sedation With Fentanyl And Midazolam: A Prospective Study 査読

D. Minami, N. Takigawa, T. Ninomiya, T. Kubo, E. Ichihara, K. Ohashi, A. Sato, K. Hotta, T. Shibayama, N. Miyahara, M. Tabata, A. Kanehiro, K. Kiura

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 195 ( 9 ) 871 - 874 2017年

IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema 査読

Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Koichi Waseda, Daisuke Morichika, Etsuko Kurimoto, Hikari Koga, Mikio Kataoka, Erwin W. Gelfand, Daniel J. Cua, Akihiko Yoshimura, Mitsune Tanimoto, Arihiko Kanehiro

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 55 ( 5 ) 697 - 707 2016年11月

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

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23(-/-)) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23(-/-) mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid ofWTmice was attenuated in IL-23(-/-) mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

DOI： 10.1165/rcmb.2016-0015OC

Heerfordt's Syndrome Associated with a High Fever and Elevation of TNF-α. 査読

Makimoto G, Miyahara N, Yoshikawa M, Taniguchi A, Kanehiro A, Tanimoto M, Kiura K

Acta medica Okayama 70 ( 4 ) 273 - 277 2016年8月

Increased Serum KL-6 Levels Induced by Pulmonary Mycobacterium Avium Complex Infection in a Patient with RA-associated Lung Disease 査読

Koichi Waseda, Kazuki Ocho, Kou Hasegawa, Kosuke Kimura, Masaya Iwamuro, Yoshihisa Hanayama, Eisei Kondo, Nobuaki Miyahara, Fumio Otsuka

ACTA MEDICA OKAYAMA 70 ( 3 ) 217 - 221 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

KL-6 is a glycoprotein found predominantly on type II pneumocytes and alveolar macrophages, and often shows increased serum levels in patients with interstitial pneumonia. We report a case of mycobacterium avium complex (MAC) infection whose disease activity was correlated with KL-6 levels in serum. During treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) with prednisolone, chest image findings improved in association with decreased KL-6 levels. Following tapering of prednisolone, chest image findings deteriorated again as levels of KL-6 increased, suggesting recurrence of RA-ILD. Bronchoscopic examination revealed active MAC infection. Treatment of MAC infection not only improved chest image findings but also decreased KL-6 levels in serum, suggesting that KL-6 was increased by active MAC infection by itself, not by recurrence of RA-ILD. To the best of our knowledge, this is the first documentation of KL-6 elevation in serum in association with active MAC infection.

DOI： 10.18926/AMO/54422

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation 査読

Katsuyuki Takeda, Nobuaki Miyahara, Shigeki Matsubara, Christian Taube, Kenichi Kitamura, Astushi Hirano, Mitsune Tanimoto, Erwin W. Gelfand

IMMUNE NETWORK 16 ( 3 ) 165 - 175 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：KOREA ASSOC IMMUNOLOGISTS

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-gamma, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

DOI： 10.4110/in.2016.16.3.165

成人気管支喘息における好酸球性中耳炎合併の実態についての検討

谷本安, 板野純子, 石賀充典, 難波史代, 田中寿明, 小野勝一郎, 高橋秀治, 濱田昇, 河田典子, 木村五郎, 宮原信明, 木浦勝行, 谷本光音, 宗田良

日本呼吸器学会誌 5 ( 増刊 ) 251 - 251 2016年3月

A case of acquired hemophilia a diagnosed in conjunction with oral bleeding 査読

Eriko Yanagi, Toshiyuki Kishi, Takao Matsumura, Yoshinori Tani, Nobuaki Miyahara

Journal of Otolaryngology of Japan 119 ( 8 ) 1133 - 1136 2016年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.

Acquired hemophilia A is a rare disease in which autoantibodies to factor VIII are present. It is often manifested as a sudden onset of a critical bleeding episode, and its incidence is reported to be 1.48 cases per million persons per year. We report herein on a case of acquired hemophilia A associated with a submucosal hematoma of the oral floor, pharynx, and larynx. A 78-year-old male presented with fresh bleeding from his mouth, associated with hematoma of the oral floor, pharynx, and larynx. Laboratory test showed that the activated partial thromboplastin time was prolonged, and the platelet count and prothrombin time were normal. Coagulation tests revealed decreased factor VIII levels, and the presence of factor VIII inhibitor. A diagnosis of acquired hemophilia A was made, and immunotherapy with corticosteroids was initiated. After treatment, the bleeding tendency was controlled. On hospital day 29, the symptoms disappeared. Although acquired hemophilia A is a rare coagulopathic condition, it should be considered as one of the differential diagnoses in a case of sudden onset of severe hemorrhagic tendency of unknown origin.

DOI： 10.3950/jibiinkoka.119.1133

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness 査読

Akihiko Taniguchi, Nobuaki Miyahara, Koichi Waseda, Etsuko Kurimoto, Utako Fujii, Yasushi Tanimoto, Mikio Kataoka, Yasuhiko Yamamoto, Erwin W. Gelfand, Hiroshi Yamamoto, Mitsune Tanimoto, Arihiko Kanehiro

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 309 ( 8 ) L789 - L800 2015年10月

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

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE(+/+)) and RAGE-deficient (RAGE(-/-)) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE(-/-) mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE(+/+) mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE(-/-) mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

DOI： 10.1152/ajplung.00087.2015

Emphysema Requires the Receptor for Advanced Glycation End-Products Triggering on Structural Cells 査読

Koichi Waseda, Nobuaki Miyahara, Akihiko Taniguchi, Etsuko Kurimoto, Genyo Ikeda, Hikari Koga, Utako Fujii, Yasuhiko Yamamoto, Erwin W. Gelfand, Hiroshi Yamamoto, Mitsune Tanimoto, Arihiko Kanehiro

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 52 ( 4 ) 482 - 491 2015年4月

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

Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end-products (RAGE) is a multiligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury. However, studies that address the role of RAGE in pulmonary emphysema are inconclusive. We investigated the role of RAGE in the development of elastase-induced pulmonary inflammation and emphysema in mice. RAGE-sufficient (RAGE(+/+)) mice and RAGE-deficient (RAGE(-/-)) mice were treated with intratracheal elastase on Day 0. Airway inflammation, static lung compliance, lung histology, and the levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage fluid were determined on Days 4 and 21. Neutrophilia in bronchoalveolar lavage fluid, seen in elastase-treated RAGE(+/+) mice, was reduced in elastase-treated RAGE(-/-) mice on Day 4, and was associated with decreased levels of keratinocyte chemoattractant, macrophage inflammatory protein-2, and IL-1 beta. Static lung compliance values and emphysematous changes in the lung tissue were decreased in RAGE(-/-) mice compared with RAGE(+/+) mice on Day 21 after elastase treatment. Experiments using irradiated, bone marrow-chimeric mice showed that the mice expressing RAGE on radioresistant structural cells, but not hematopoietic cells, developed elastase-induced neutrophilia and emphysematous change in the lung. In contrast, mice expressing RAGE on hematopoietic cells, but not radioresistant structural cells, showed reduced neutrophilia and emphysematous change in the lung. These data identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.

DOI： 10.1165/rcmb.2014-0027OC

肺腺癌に合併し診断に苦慮した続発性クリプトコッカス症の2例

森近大介, 南大輔, 二宮貴一郎, 入江真大, 葉山牧夫, 山本寛斎, 堀田勝幸, 宮原信明, 田端雅弘, 三好新一郎, 谷本光音, 木浦勝行

気管支学 36 ( 2 ) 210 - 210 2014年3月

Effect of a Cysteinyl Leukotriene Receptor Antagonist on Experimental Emphysema and Asthma Combined with Emphysema 査読

Genyo Ikeda, Nobuaki Miyahara, Hikari Koga, Yasuko Fuchimoto, Koichi Waseda, Etsuko Kurimoto, Akihiko Taniguchi, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Arihiko Kanehiro

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 50 ( 1 ) 18 - 29 2014年1月

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

The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT(1)R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT(1)R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT(1)R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

DOI： 10.1165/rcmb.2012-0418OC

Invasive Mucinous Adenocarcinoma Mimicking Organizing Pneumonia Associated with Mycobacterium fortuitum Infection 査読

Daisuke Morichika, Nobuaki Miyahara, Katsuyuki Hotta, Yoshiko Okamoto, Daisuke Minami, Masahiro Irie, Yasushi Tanimoto, Arihiko Kanehiro, Mitsune Tanimoto, Katsuyuki Kiura

INTERNAL MEDICINE 53 ( 24 ) 2795 - 2799 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum. The patient's lung consolidation rapidly progressed; however, repeated bronchoscopy showed no atypical cells, thus suggesting a diagnosis of organizing pneumonia associated with M. fortuitum infection. However, the surgical biopsy specimen was diagnostic for adenocarcinoma, with no mycobacterial infection. Invasive mucinous adenocarcinoma should not be excluded in the differential diagnosis of patients with clinical features of organizing pneumonia and nontuberculous mycobacterium infection, even if a transbronchial biopsy confirms the absence of malignancy.

DOI： 10.2169/internalmedicine.53.2783

Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: Neutrophil elastase inhibition attenuates allergic airway responses 査読

Hikari Koga, Nobuaki Miyahara, Yasuko Fuchimoto, Genyo Ikeda, Koichi Waseda, Katsuichiro Ono, Yasushi Tanimoto, Mikio Kataoka, Erwin W. Gelfand, Mitsune Tanimoto, Arihiko Kanehiro

Respiratory Research 14 ( 1 ) 8 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice.Methods: BALB/c mice were sensitized and challenged (primary) with ovalbumin (OVA). Six weeks later, a single OVA aerosol (secondary challenge) was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge.Results: Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN) T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-β1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice.Conclusion: These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the neutrophil elastase inhibitor reduced AHR to inhaled methacholine indicating the potential for its use as a modulator of the immune/inflammatory response in both the neutrophil- and eosinophil-dominant phases of the response to secondary allergen challenge. © 2013 Koga et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1465-9921-14-8

IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice 査読

Etsuko Kurimoto, Nobuaki Miyahara, Arihiko Kanehiro, Koichi Waseda, Akihiko Taniguchi, Genyo Ikeda, Hikari Koga, Hisakazu Nishimori, Yasushi Tanimoto, Mikio Kataoka, Yoichiro Iwakura, Erwin W. Gelfand, Mitsune Tanimoto

Respiratory Research 14 ( 1 ) 5 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear.Methods: In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.Results: Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.Conclusions: These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression. © 2013 Kurimoto et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1465-9921-14-5

Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses 査読

Hikari Koga, Nobuaki Miyahara, Yasuko Fuchimoto, Genyo Ikeda, Koichi Waseda, Katsuichiro Ono, Yasushi Tanimoto, Mikio Kataoka, Erwin W. Gelfand, Mitsune Tanimoto, Arihiko Kanehiro

RESPIRATORY RESEARCH 14 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Background: Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice.
Methods: BALB/c mice were sensitized and challenged (primary) with ovalbumin (OVA). Six weeks later, a single OVA aerosol (secondary challenge) was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge.
Results: Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN) T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-beta 1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice.
Conclusion: These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the neutrophil elastase inhibitor reduced AHR to inhaled methacholine indicating the potential for its use as a modulator of the immune/inflammatory response in both the neutrophil-and eosinophil-dominant phases of the response to secondary allergen challenge.

DOI： 10.1186/1465-9921-14-8

A Definite Case of L-carbocisteine-induced Pneumonia with CATCH22 Syndrome 査読

Kenichiro Kudo, Eiki Ichihara, Akiko Hisamoto, Katsuyuki Hotta, Nobuaki Miyahara, Yasushi Tanimoto, Sadaharu Akagi, Katsuya Kato, Mitsune Tanimoto, Katsuyuki Kiura

INTERNAL MEDICINE 52 ( 1 ) 97 - 100 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

A 32-year-old male with CATCH22 syndrome presented with a high fever and productive cough after taking drugs for acute bronchitis, including L-carbocisteine. Chest radiography revealed ground-glass opacities in the bilateral lung fields. He had a history of similar pneumonia. Under the assumption of drug-induced pneumonia, or bacterial or viral pneumonia, all drugs including L-carbocisteine were discontinued, and antibiotics were started. A drug-induced lymphocyte stimulation test was positive only for L-carbocisteine. The only drug in common between this and the previous episode of pneumonia was L-carbocisteine. We thus concluded that this was a definite case of L-carbocisteine-induced pneumonia in a patient with CATCH22 syndrome.

DOI： 10.2169/internalmedicine.52.7882

[Bronchial asthma and allergic diseases]. 査読

Miyahara N, Kiura K

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 8 545 - 549 2012年11月

　前のページ - 次のページ　

1
2
3
4
5
6
7
8
9