Bronchiolar epithelial catalase is diminished in smokers with mild COPD

被引:22
作者
Betsuyaku, Tomoko [1 ]
Fuke, Satoshi [2 ]
Inomata, Takashi [2 ]
Kaga, Kichizo [3 ]
Morikawa, Toshiaki [3 ]
Odajima, Nao [2 ]
Adair-Kirk, Tracy [4 ,5 ]
Nishimura, Masaharu [2 ]
机构
[1] Keio Univ, Sch Med, Div Pulm Med, Dept Med, Tokyo 1608582, Japan
[2] Hokkaido Univ, Sch Med, Dept Med 1, Sapporo, Hokkaido 060, Japan
[3] Hokkaido Univ, Sch Med, Dept Surg Oncol, Sapporo, Hokkaido 060, Japan
[4] Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA
[5] Barnes Jewish Hosp, St Louis, MO 63110 USA
关键词
OBSTRUCTIVE PULMONARY-DISEASE; CIGARETTE-SMOKE; AIRWAY EPITHELIUM; GENE-EXPRESSION; INCREASED SUSCEPTIBILITY; INDUCED EMPHYSEMA; PATHOGENESIS; MACROPHAGES; INDUCTION; FIBROSIS;
D O I
10.1183/09031936.00058912
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
This study aimed to investigate bronchiolar catalase expression and its relationship with smoking and/or chronic obstructive pulmonary disease (COPD) in humans and to determine the dynamic change of bronchiolar catalase expression in response to cigarette smoke in mice. Lung tissue was obtained from 36 subjects undergoing surgery for peripheral tumours, consisting of lifelong nonsmokers and smokers with or without COPD. Male C57BL/6 mice were subjected to cigarette smoke exposure for up to 3 months followed by a 28-day cessation period. We quantified bronchiolar catalase mRNA using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction. C22 club cells (Clara cells) in culture were exposed to cigarette smoke extract and monitored for viability when catalase expression was decreased by siRNA. Catalase was decreased at mRNA and protein levels in bronchiolar epithelium in smokers with COPD. In mice, bronchiolar catalase is temporarily upregulated at 1 day after cigarette smoke exposure but is downregulated by repeated cigarette smoke exposure, and is not restored long after withdrawal once emphysema is developed. Decreasing catalase expression in C22 cells resulted in greater cigarette smoke extract-induced cell death. Bronchiolar catalase reduction is associated with COPD. Regulation of catalase depends on the duration of cigarette smoke exposure, and plays a critical role for protection against cigarette smoke-induced cell damage.
引用
收藏
页码:42 / 53
页数:12
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