Hepatic ischemia-reperfusion injury (IRI) could result in severe liver damage and dysfunction during liver surgery and transplantation. As one of the Interferon (IFN)-stimulated genes, IFIT3 exerted antitumor activity but its roles in hepatic IRI are still unknown. In this study, roles of IFIT3 in hepatic IRI were investigated using a mouse hepatic IRI model and a cellular hypoxia-reoxygenation model. Firstly, our results showed that IFIT3 was up-regulated in reperfused liver tissues of patients undergoing liver transplantation and was positively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Secondly, knockdown of IFIT3 could significantly ameliorate hepatic IRI and suppress ischemia and reperfusion-induced release of inflammatory cytokines in vivo and in vitro. Furthermore, knockdown of IFIT3 inhibited phosphorylation of STAT1 and STAT2, and decreased expressions of IFN-stimulated genes induced by ischemia and reperfusion in vivo and in vitro. These data highlight the importance and potential clinical use of IFIT3 in hepatic IRI.
Keywords: IFIT3; Inflammation; Interferon signaling; Interferon-stimulated gene; Ischemia-reperfusion injury.
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