Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p38 MAPK and NF-κB.

Abstract

Objectives: 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 AZD0530. Pulmonary function, pathological appearance, and inflammatory factors were assessed in rats with COPD.

Results: AZD0530 significantly ameliorated pulmonary function and improved the pathological manifestations of COPD in rats. AZD0530 decreased MCP-1 and CD68 expression in lung tissues, reduced inflammatory cell accumulation, and decreased TNF-α and IL-6 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-6 secretion in the human bronchial epithelial cell line BEAS-2B. Furthermore, inhibition of Fyn by either the inhibitor or siRNA Fyn reduced the phosphorylation of p38 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 p38 MAPK and NF-κB signaling pathways. Fyn might be a promising therapeutic target for COPD.