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.

Automated summary

This study found that preintervention with resveratrol ameliorated hepatic injury and neutrophil inflammatory responses in hepatic ischemia-reperfusion injury (HIRI). Resveratrol inhibited neutrophil functions such as survival, cell cycle, migration, and chemotaxis, as well as oxidative stress and secretion of proinflammatory cytokines. The mechanism of action involved the inhibition of endothelin 1 autocrine signaling through the suppression of the ERK pathway.