Effect of acute inflammation induced by lipopolysaccharide on Fas-mediated hepatocyte apoptosis in mice

BACKGROUND: Fas/Fas ligand (FasL) apoptotic pathway in hepatocytes is thought to be involved in the pathogenesis of liver disease such as viral hepatitis and nonalcoholic steatohepatitis. Although it is known that various immune mediators modulate hepatocyte susceptibility to Fas/FasL- mediated apoptosis, the exact effects of pro- inflammatory cytokines on the apoptotic processes in hepatocyte are still not well understood. In our study we aimed to investigate the effect of acute inflammatory response on Fas/FasL-mediated hepatocyte apoptosis using a model of lipopolysaccharide (LPS)-induced acute inflammation. METHODS: Acute inflammation was induced in male C57BL/6 mice by intraperitoneal injection of LPS (0.1 µg/g body weight in 10 µL/g body weight of sterile saline) while the control group of animals received the same volume of sterile saline. After 2.5 hours both groups were treated with anti-Fas activating antibody (0.1 μg/g body weight, intravenously) in order to induce hepatocyte apoptosis. Mice were sacrificed after additional 6 hours and plasma (ALT, AST) and liver tissue (pathohistology, caspase activity assays, qPCR) were collected for the analyses. RESULTS: Mice pre-treted with LPS had lower levels of ALT (32 ± 11 vs 164 ± 61 U/L, p