Cigarette smoke affects IL-17A, IL-17F and IL-17 receptor expression in the lung tissue of COPD patients: Ex vivo/in vitro studies

Introduction: IL-17A and IL-17F target structural and inflammatory cells by IL-17R.Th-17 cytokines are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke is a risk factor for COPD. Aim: To evaluate the role of cigarette smoke on the expression of IL-17A, IL-17F and IL-17R in central and distal airways of COPD patients. Methods: The epithelial and sub-epithelial immunoreactivity for IL-17A, IL-17F and IL-17R was assessed in surgical specimens from COPD patients (n=15), healthy smokers (HS) (n=10) and from healthy subjects (HC) (n=10) by immunohistochemistry. In vitro, human bronchial epithelial cell line 16HBE, human alveolar basal epithelial cell line A549 and peripheral blood mononuclear cells (PBMC) from normal donors were stimulated with cigarette smoke extract (CSE) (0, 2.5, 5, 10%) to evaluate the IL-17A, IL-17F and IL-17R expression by flow-cytometry. Results: In central airways, immunoreactivity of IL-17A, IL-17F and IL-17R significantly increased in the epithelium of COPD and HS than in HC and IL-17A and IL-17F significantly increased in subepithelium of COPD than in HS and HC. In distal airways, immunoreactivity of IL-17A, IL-17F and IL-17R significantly increased in the epithelium and subepithelium of COPD than in HS and HC. However in distal airways, a trend toward higher levels was observed in HS than in HC. Finally, CSE significantly increased IL-17A, IL-17F and IL-17R expression in 16HBE, A549 and PBMC. Conclusions: Increased expression of IL-17A, IL-17F and IL-17R might be triggered by cigarette smoke, affecting lung epithelial and inflammatory cells in lung tissue of COPD patients.