コンドウ　ミツコ   KONDO Mitsuko   近藤　光子    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice.
掲載誌名	正式名：The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 略　 称：Eur Respir J ISSNコード：09031936/13993003
巻・号・頁	35(5),pp.1164-1171
著者・共著者	Arai N† Kondo M, Izumo T, Tamaoki J, Nagai A*.
担当区分	2nd著者
発行年月	2010/05
概要	Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro. On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human NE. Bronchoalveolar lavage fluid (BALF) and lung sections were analysed on days 8, 11 and 14. The effect of late administration of tiotropium on the goblet cell metaplasia by NE aspiration was also assessed. NE-induced MUC5AC production by NCI-H292 cells was measured with ELISA. Repeated NE aspiration induced marked goblet cell metaplasia. The grading of goblet cell metaplasia, neutrophil count and eosinophil count in BALF, keratinocyte-derived chemokine level and leukotriene B(4) level in BALF, and M(3) receptor expression by immunohistochemistry, were lower in the tiotropium group than in the vehicle group. Late administration of tiotropium inhibited the established goblet cell metaplasia. Tiotropium inhibited NE-induced MUC5AC production. Tiotropium inhibited NE-induced goblet cell metaplasia and mucin production, probably mediated by suppression of inflammation and a direct action on epithelial cells. This result suggests that tiotropium may be useful for the treatment of mucus overproduction in COPD.
DOI	10.1183/​09031936.00040709