IL-17A and GDF15 are able to induce epithelial-mesenchymal transition of lung epithelial cells in response to cigarette smoke

Smoking is one of the primary causes of chronic obstructive pulmonary disease (COPD). Sustained active epithelial-mesenchymal transition (EMT) in COPD may explain the core pathophysiology of airway fibrosis and why lung cancer is so common among smokers. Interleukin (IL)-17A and growth/differentiation factor (GDF)15 have been reported to be biomarkers of COPD; however, the role of IL-17A and GDF15 in EMT remains unclear. The aim of the present study was to investigate the role of IL-17A and GDF15 in the pathogenesis of COPD. It was demonstrated that IL-17A and GDF15 are upregulated in patients with COPD, particularly those with a history of smoking. The results also revealed that IL-17A and GDF15 expression was negatively correlated with the epithelial marker epithelial-cadherin and positively correlated with the mesenchymal marker vimentin. Furthermore, treatment with cigarette smoke extract or IL-17A induced GDF15 expression. Combined treatment with IL-17A and GDF15 induced EMT in human small epithelial HSAEpiC cells in vitro. Collectively, the results of the present study suggest that IL-17A and GDF15-induced EMT serves an important role in the pathology of COPD.