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.

持续性炎症是非酒精性脂肪肝发展为肝硬化和肝癌的主要原因之一，减少炎症因子的表达可能是缓解非酒精性脂肪性肝炎（NASH）发展的有效策略。SIGIRR是白细胞介素1受体家族的成员，已显示出抑制炎性细胞因子的产生，其下调或缺失被认为是引起器官发炎性损伤的重要原因。在这项研究中，我们确定白藜芦醇有效诱导了SIGIRR启动子的转录活性，并且还增加了人肝细胞和小鼠肝脏中SIGIRR mRNA的水平。此外，研究了白藜芦醇对蛋氨酸/胆碱缺乏饮食诱导的NASH小鼠模型的潜在影响。白藜芦醇维持了小鼠肝脏中SIGIRR的表达水平。白藜芦醇干预减轻了NASH的进展；降低了丙氨酸转氨酶和天冬氨酸转氨酶的水平；并下调了肿瘤坏死因子-α，白介素（IL）-6，IL-1β和转化生长因子-β的mRNA和蛋白质水平。此外，增加的SIGIRR可能会阻断Toll样受体/核因子-κB信号通路的活性体内和体外。在体外，白藜芦醇预处理可防止由泡沫巨噬细胞释放的炎性细胞因子引起的肝细胞损伤，所述炎性细胞因子与NASH的发展有关。但是，白藜芦醇在炎性细胞因子微环境中不能有效诱导肝细胞SIGIRR基因转录。总之，白藜芦醇是实用的，并且是SIGIRR蛋白的激动剂，可负调节肝脏中炎症因子的表达，这表明适量摄入可能是预防NASH发生和发展的潜在途径。