ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells

Abstract

Lung epithelial apoptosis and inflammatory responses are important pathological processes in many pulmonary disorders. ResolvinD1 (RvD1), generated in inflammatory resolution processes, reduces inflammatory responses in animal models of lung diseases. The aim of this study was to investigate whether RvD1 attenuates apoptosis and proinflammatory responses in primary human alveolar epithelial type 2 cells (AEC2 cells) that are exposed to lipopolysaccharide (LPS) in vitro. We examined the percentage of apoptotic AEC2 cells by flow cytometry. The expression levels of cytokines and chemokines were determined by ELISA and microarray. The expression levels of molecular signaling modulators were evaluated by western blot. LPS-stimulated AEC2 cells pretreated with RvD1 exhibited a statistically significant reduction in apoptosis. The pretreatment of LPS-stimulated cells with RvD1 stimulated the phosphorylation of AKT and prevented the cleavage of caspase-3, the upregulation of Bax, and the downregulation of Bcl-2. The antiapoptotic effects of RvD1 were abrogated upon pretreatment with a PI3K inhibitor. In addition, RvD1 reduced the release of cytokines and chemokines, and inhibited the degradation and phosphorylation of IκB-α in LPS-stimulated AEC2 cells. RvD1 reduces apoptosis of LPS-exposed AEC2 cells by inducing the phosphorylation of AKT and attenuates the inflammatory response by suppressing the degradation and phosphorylation of IκB-α.