Epithelium-derived IL17A Promotes Cigarette Smoke-induced Inflammation and Mucus Hyperproduction

In this study, we aim to determine whether epithelial-derived IL17A regulates inflammation and mucus hyperproduction in COPD using a cultured human bronchial epithelial (HBE) cell line in vitro and airway epithelium IL17A-specific knockout mouse in vivo. Increased IL17A expression was observed in mouse airway epithelium upon cigarette smoke (CS) exposure or in a COPD mouse model that was induced by CS and elastin. CS extract (CSE) also triggered IL17A expression in HBE cells. Blocking IL17A or IL17RA effectively attenuated CSE-induced MUC5AC and the inflammatory cytokines IL6, tumor necrosis factor (TNF)-α, and IL1β in HBE cells, suggesting that IL17A mediates CSE-induced inflammation and mucin production in an autocrine manner. CSE activated p-JUN and p-JNK, which were also reduced by IL17RA-siRNA, and JUN-siRNA attenuated CSE-induced IL6 and MUC5AC. In vivo, selective knockout of IL17A in airway epithelium markedly reduced the neutrophilic infiltration in Bronchoalveolar Lavage Fluid (BALF), peribronchial inflammation, pro-inflammatory mediators (CXCL1 and CXCL2), and mucus production in a COPD mouse model. We showed a novel function of airway epithelium-derived IL17A, which can act locally in an autocrine manner to amplify inflammation and increase mucus production in COPD pathogenesis.PMID:34186014 | DOI:10.1165/rcmb.2020-0424OC

Source: Respiratory Care - June 29, 2021 Category: Respiratory Medicine Authors: Mindan Wu Tianwen Lai Du Jing Shiyi Yang Yanping Wu Zhouyang Li Yinfang Wu Yun Zhao Lingren Zhou Haipin Chen Jiaxin Shen Wen Li Songmin Ying Zhihua Chen Xiaohong Wu Huahao Shen Source Type: research