Chitinase 3-like 1 regulates IL-8 expression in airway epithelial cells

Abstract

Background: Viral respiratory infection is a leading cause of inflammatory lung disease and mortality. Interleukin (IL)-8, one of the critical inflammatory mediators, has been suggested to induce inflammation against viral infections. Chitinase 3-like 1 (CHI3L1), which belongs to 18-glycosylhydrolase family, contributes to airway inflammation. However, it remains unclear that the role of CHI3L1 in the expression of IL-8 caused by viral infections. Thus, this study was to investigate the role of CHI3L1 in the regulation of IL-8 expression, which was caused by viral infections in bronchial epithelial cells. Methods: Human bronchial epithelial cell line, BEAS-2B, was stimulated with a synthetic analog of viral double-stranded RNA, polyinosinic : polycytidylic acid (poly(I:C)). To explore the role of CHI3L1 in viral infection, CHI3L1 knock-down was performed in BEAS-2B cells by shRNA lentiviral transduction. The expression of CHI3L1 and pro-inflammatory cytokines such as IL-8, and phosphorylation of mitogen-activated protein kinase (MAPK) pathways were analyzed. BEAS-2B cells were infected with human respiratory syncytial virus (RSV) A2 strain and the expression levels of CHI3L1 and IL-8 were analyzed. Results: Stimulation of BEAS-2B cells with poly(I:C) increased expression of CHI3L1 and IL-8. However, IL-8 expression was abrogated in CHI3L1 knock-down BEAS-2B cells. Poly(I:C) stimulation of BEAS-2B cells resulted in phosphorylation of MAPK pathways, and inhibitions of MAPK pathways significantly abolished IL-8 secretion. The phosphorylation of MAPK pathways was also diminished in CHI3L1 knock-down BEAS-2B cells. In addition to poly(I:C), infection with RSV increased the expression levels of CHI3L1 and IL-8. The expression of IL-8 induced by RSV infection was abrogated in CHI3L1 knock-down BEAS-2B cells. Conclusion: This study suggests that CHI3L1 is involved in IL-8 secretion by regulating MAPK pathways during viral infections in bronchial epithelial cells.