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ID 51466
フルテキストURL
著者
Koga, Hikari Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Miyahara, Nobuaki Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Fuchimoto, Yasuko Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Ikeda, Genyo Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Waseda, Koichi Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Ono, Katsuichiro Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Tanimoto, Yasushi Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Kataoka, Mikio Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Gelfand, Erwin W. Natl Jewish Hlth, Dept Pediat, Div Cell Biol
Tanimoto, Mitsune Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Kanehiro, Arihiko Okayama Univ, Dept Hematol Oncol Allergy & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
抄録
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.
キーワード
Neutrophil
Elastase
Airway
Hyperresponsiveness
Asthma
発行日
2013-01-24
出版物タイトル
Respiratory Research
14巻
出版者
Biomed Central Ltd
ISSN
1465-993X
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1186/1465-9921-14-8
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/51447
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT