Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p۳۸ MAPK and NF-κB

Objective(s): The current research was conducted to study the function of Fyn in a rat model of chronic obstructive pulmonary disease (COPD).Materials and Methods: COPD in rats was induced by intratracheal instillation of lipopolysaccharide and long-term exposure to cigarette smoke. Subsequently, the rats were treated with the Fyn-specific inhibitor AZD۰۵۳۰. Pulmonary function, pathological appearance, and inflammatory factors were assessed in rats with COPD.Results: AZD۰۵۳۰ significantly ameliorated pulmonary function and improved the pathological manifestations of COPD in rats. AZD۰۵۳۰ decreased MCP-۱ and CD۶۸ expression in lung tissues, reduced inflammatory cell accumulation, and decreased TNF-α and IL-۶ production in bronchoalveolar lavage fluid. In an in vitro study, pharmacological inhibition of Fyn or knockdown of Fyn by siRNA inhibited lipopolysaccharide- and cigarette smoke extract-induced TNF-α and IL-۶ secretion in the human bronchial epithelial cell line BEAS-۲B. Furthermore, inhibition of Fyn by either the inhibitor or siRNA Fyn reduced the phosphorylation of p۳۸ MAPK- and NF-κB-related molecules, which strongly affected the occurrence of inflammatory responses.Conclusion: Collectively, these data show that Fyn promotes COPD development by modulating the p۳۸ MAPK and NF-κB signaling pathways. Fyn might be a promising therapeutic target for COPD.

کلیدواژه ها:

AZD۰۵۳۰و Chronic obstructive pulmonary disease ، Fyn ، MAPK ، NF-κB