Abstract
Persistent inflammation is one of the main reasons that nonalcoholic fatty liver disease develops into cirrhosis and liver cancer, and reducing the expression of inflammatory factors may be an effective strategy to alleviate the development of nonalcoholic steatohepatitis (NASH). SIGIRR, a member of the interleukin-1 receptor family, has been shown to inhibit the production of inflammatory cytokines, and its down-regulation or deletion has been suggested to be an important cause of inflammatory damage to organs. In this study, we identified that resveratrol efficiently induced the transcriptional activity of the SIGIRR promoter and also increased SIGIRR mRNA levels in human hepatocytes and mouse livers. Furthermore, the potential effects of resveratrol on a methionine/choline-deficient diet-induced NASH mouse model were investigated. Resveratrol maintained the expression level of SIGIRR in the mouse liver. Resveratrol intervention alleviated NASH progression; decreased the levels of alanine aminotransferase and aspartate aminotransferase; and down-regulated tumor necrosis factor-α, interleukin (IL)-6, IL-1β and transforming growth factor-β mRNA and protein levels. Additionally, increased SIGIRR potentially blocked the activity of the Toll-like receptor/nuclear factor-κB signaling pathway both in vivo and in vitro. In vitro, resveratrol pretreatment protected against hepatocyte injury caused by foamy macrophage-released inflammatory cytokines, which are involved in the development of NASH. However, resveratrol did not effectively induce hepatocyte SIGIRR gene transcription in the inflammatory cytokine microenvironment. In conclusion, resveratrol is practical and acts as an agonist of the SIGIRR protein to negatively regulate the expression of inflammatory factors in liver, suggesting that appropriate intake may be a potential way to prevent the occurrence and development of NASH.