Immunomodulatory Effect Of Inflammasome In The Innate Immunity Of Liver And Its Mechanistic Insights

The activation of inflammasome is a common pathophysiological process in the process of liver injury. We build two models of liver injury, ischemia-reperfusion(IR) injury and bile duct ligation(BDL), to verify that inflammasome are activated in the both models. Then we apply two drugs to elaborated their effect on the regulation of innate immunity from different aspects.The Chinese herb preparation Xuebijing injection(XBJ) has been widely used in the management of various septic disorders or inflammation-related conditions, however the molecular mechanism of its anti-inflammatory effect remains largely elusive. In the current study, we found that XBJ treatment potently ameliorated mouse hepatic ischemia-reperfusion(IRI), manifested as decreased liver function tests(LDH, ALT, AST), improved inflammation and less hepatocyte apoptosis. Notably, XBJ markedly inhibited inflammasome activation and IL-1 production in mouse livers subjected to IR, even in the absence of Kupffer cells, suggesting Kupffer cells are not necessary for hepatic inflammasome activation upon Redox-induced sterile inflammation. This finding led us to investigate the role of XBJ on hepatocyte apoptosis and inflammasome activation using an in vitro hydrogen peroxide(H2O2)-triggered hepatocyte injury model. Our data clearly demonstrated that XBJ potently inhibited apoptosis, as well as caspase-1 cleavage and IL-1β production in a time- and dose-dependent manner in isolated hepatocytes, suggesting that in addition to its known modulatory effect on NF-ΚB-dependent inflammatory gene expression, it also has a direct impact on hepatocyte inflammasome activation. The current study not only deepens our understanding of how XBJ ameliorates inflammation and apoptosis, but also has immediate practical significance in many clinical situations such as partial hepatectomy, liver transplantation, etc.Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors(V1R). Its hepatoprotective effects have not been specifically investigated. The liver function of patients were assessed before and after the treatment of terlipressin. ALT and AST decreased and ALB increased after terlipressin. Terlipressin administration may be a novel approach for the treatment in patients with end-stage liver diseases(ESLDs).