IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability.

Chao Cao,Huahao Shen,Wen Li,Zhiwei Xu,Xinwei Geng,Hongbin Zhou,Zhengqiang Bao,Zhihua Chen,Tianwen Lai,Songmin Ying,Baoping Tian,Yanping Wu

doi:10.3390/cells10051173

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.

Highlights

It is well known that chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer [1]
Recent studies further showed that IL-17A is essential for small airway fibrosis and inflammation in mice exposed to cigarette smoke, suggesting a role for this cytokine in airway obstruction during COPD [7]
We investigated the expression of IL-17 in smokers and non-smokers

Summary

Introduction

It is well known that chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer [1]. Both COPD and lung cancer are primarily caused by cigarette smoke (CS), and are frequently presented as co-morbidities [1,2]. DNA repair plays a fundamental role in the maintenance of genomic stability against the threats posed by both exogenous and endogenous stress. This process prevents the accumulation of DNA damage and its detrimental consequences for chromosomal rearrangements, sensitivity to genotoxins, and cell viability [4].

Results

Discussion

Conclusion