Cystic fibrosis transmembrane regulator inhibits cigarette smoke-induced COPD via activation of chlo

• 作 者: DefuLi;HuaJiang;ZhengtuLi;ChristineBear;NanshanZhong;WenjuLu;XuefangGong;JianWang;WenliangZhou;JiazeShu;XiaomingXu;ChentingZhang;ChuyiXu;YanWang;
• 机 构: State Key Laboratory of Respiratory Diseases,Guangzhou Institute of Respiratory Disease,The First Af
• 出 处: 中华医学会第七次全国高原医学学术会议暨中国病理生理学会第九次全国缺氧和呼吸病理生理学术会议
• 发表日期: 2014年期

　　Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) embody multiple pathological features in common, such as chronic airway inflammation.The dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) is causal to CF; however, its relationship to COPD has not been defined.In this study, we determined the role and signaling of CFTR in modulating cigarette smoke (CS)-induced COPD development.We found that the expression and function of CFTR was decreased in COPD mouse lung.Inhibition of CFTR by its inhibitor inh-172 potentiated mouse lung inflammation and lung function decline induced by CS.Exposure to cigarette smoke extract (CSE) led to reduced expression of CFTR, increased releases of IL-6 and-8, and greater activation of ERK1/2 and Nrf-2 in 16HBE airway epithelial cells.The CSE-induced changes of IL-6,-8, ERK1/2 and Nrf-2 were reinforced by inh-172 pretreatment.Inhibition of ERK1/2 attenuated CSE-indueed Nrf-2 activation.Knockdown of Nrf-2 by siRNA inhibited, whereas activation of Nrf-2 enhanced CSE-induced IL-6 and-8 releases by 16HBE cells.