Resveratrol alleviates sepsis-induced acute lung injury by suppressing inflammation and apoptosis of alveolar macrophage cells

Sepsis is a major cause of death in intensive care units. The purpose of this study was to investigate the effect of resveratrol (RSV) on sepsis-induced acute lung injury (ALI). The underlying molecular mechanisms were deciphered by both in vitro and in vivo experiments. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP). RSV pretreatment significantly attenuated CLP-induced acute lung injury, which was associated with enhanced expression of VEGF-B. The protective properties of RSV were assayed in lipopolysaccharide (LPS)-stimulated MH-S cells. We determine that RSV administration inhibited the increased production of TNF-α, IL-6, and IL-1β in LPS-stimulated MH-S cells, which was associated with inhibition of the nuclear factor-κB, P38, and ERK signaling pathways. We also provide evidence that RSV administration reduced LPS-induced apoptosis of MH-S cells by altering the unbalance of Bax/Bcl-2 and inhibiting LPS-induced autophagy. The inhibitory effects of RSV on cytokine levels and apoptosis of alveolar macrophages were both blocked by VEGF-B siRNA. Furthermore, RSV administration regulated LPS-induced C5aR and C5L2 expression, revealing an additional mechanism underlying RSV’s anti-inflammatory and anti-apoptosis effects. Collectively, these results demonstrated that RSV was able to protect against sepsis-induced acute lung injury by activating the VEGF-B signaling pathway.