Resveratrol improves hepatic ischemia-reperfusion injury by inhibiting neutrophils via the ERK signaling pathway.

Hepatic ischemia-reperfusion injury (HIRI) is the main complication and even mortality in the setting of hepatic surgery or transplantation. Inflammation, especially the neutrophil response, plays important roles during the process of HIRI. In this study, we found that resveratrol preintervention ameliorated IRI-induced hepatic injury and neutrophil inflammatory responses in the liver. Moreover, RNA-sequencing analysis showed that resveratrol inhibited the functions of neutrophils, such as survival, cell cycle, migration and chemotaxis, oxidative stress and secretion of proinflammatory cytokines. Resveratrol restrained oxidative stress and the inflammatory response of neutrophils via inhibition of endothelin 1 autocrine signaling by suppressing the ERK signaling pathway. These data provide more evidence for the immunomodulatory role of resveratrol and enrich our understanding of immune strategies to improve HIRI. Resveratrol preintervention ameliorated IRI-induced hepatic injury and neutrophil inflammatory responses. Mechanistically, resveratrol restrained neutrophils proinflammation via inhibition of endothelin 1 autocrine signaling by suppressing the ERK signaling pathway. [Display omitted] • Resveratrol intervention ameliorates hepatic ischemia-reperfusion injury (HIRI). • Resveratrol inhibits neutrophils survival and inflammation responses in HIRI. • Resveratrol suppresses neutrophils via inhibition on their endothelin 1 autocrine. • Resveratrol inhibits neutrophil endothelin 1 secretion through ERK/c-Fos pathway. [ABSTRACT FROM AUTHOR]