IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability
Chao Cao, Baoping Tian, Xinwei Geng, Hongbin Zhou, Zhiwei Xu, Tianwen Lai, Yanping Wu, Zhengqiang Bao, Zhihua Chen, Wen Li, Huahao Shen, Songmin Ying
Abstract
(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.