Downregulation of miR-155 attenuates sepsis-induced acute lung injury by targeting SIRT1.

Sepsis-induced acute lung injury (ALI) characterized by devastating hyperinflammatory response in the lungs is the ultimate cause of high mortality and mobility in septic patients. miR-155 was reported to be significantly upregulated in sepsis-induced ALI cases and alleviated inflammation in septic lung injury in mouse and cell models. However, the detailed role of miR-155 and its underlying mechanism in sepsis-associated ALI remain to be further explored. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was successfully established. miR-155 expression was significantly higher in CLP mice compared with control mice. miR-155 inhibitor attenuated histopathological changes, lung apoptosis, lung inflammation, and increased the survival rate in CLP-induced ALI mice. In vitro, miR-155 expression increased in murine alveolar epithelial cells MLE-12 stimulated with lipopolysaccharide (LPS) and downregulation of miR-155 suppressed apoptosis and the release of inflammatory cytokines in LPS-stimulated MLE-12 cells. In addition, luciferase reporter assay and RNA immunoprecipitation (RIP) demonstrated that SIRT1 was a direct target of miR-155 in LPS-treated MLE-12 cells. Moreover, miR-155 partially reversed the inhibitory effects of SIRT1 on apoptosis and inflammatory response in LPS-stimulated MLE-12 cells. In summary, these results demonstrated that downregulation of miR-155 attenuated sepsis-induced ALI in vivo and in vitro by targeting SIRT1. IJCEP