The liver inflammation check details and injury in 3xTg-iHAP mice were spontaneously resolved through liver regeneration and restitution within 5 days after low-dose Dox challenging. Taken together, we have developed and validated a new murine model of hepatocyte apoptosis-induced sterile liver inflammation and wound healing response. In a pilot study, we further revealed that 3xTg-iHAP mice chronically fed with alcohol-containing Lieber-DeCarli liquid diet developed profound steatohepatitis after treatment with a single low-dose of Dox. This finding suggests that our novel mouse model for sterile liver inflammation

can be combined with other liver disease models for studying the exact role of multi-hits in the pathogenesis of numerous inflammatory liver diseases such as alcoholic hepatitis and nonalcoholic steatohepatitis. Thus, 3xTg-iHAP mice is a novel in vivo research tool and may have a broad range of applications from exploring insights into the pathogenesis of sterile liver inflammation to testing new therapies for various liver diseases and complications (Supported in part by grants from the NIH). The following people have nothing to disclose: Heng-Fu Bu, Fangyi Liu, Xiao Wang, Pauline M. Chou, Catherine Marek, Ke Tian, Peng

Wang, Hua Geng, M. S. Rao, Suhail Akhtar, Monique E. De Paepe, Xiao-Di Tan Background/Aims: Nerve growth factor (NGF) has pro-inflammatory effects in lung and skin inflammatory diseases. During liver regeneration, NGF secreted learn more by hepatocytes

induces hepatic stellate cell apoptosis. However, NGF involvement in models of liver damage and inflammation has not yet been assessed. We investigated the possible inflammatory effects of NGF on isolated hepatic stellate cells (HSC), as well as the in vivo effect of silencing NGF on acute liver damage and inflammation. Methods: Primary HSC from rats and mice were isolated and cultured for 7d and 14d to CYTH4 obtain activated and fully activated HSC, respectively. HSC were treated with 100ng/ ml NGF and proNGF and inflammatory cytokine expression was assessed by qRT-PCR and ELISA. Acute liver damage was induced by two i.p. injections of CCl4 (1 μl/g body weight) or by bile duct ligation (BDL) and mice received daily treatment with antisense oligodeoxynucleotide to NGF (ODN)(25mg/kg body weight). Results: Both NGF and proNGF induced expression of pro-inflammatory cytokines TNFα and IL-6 in activated and fully activated primary rat and murine HSC. Administration of antisense ODN to NGF in the acute CCl4 and BDL models reduced liver damage, as demonstrated by significantly reduced serum liver enzymes. In addition, antisense ODN to NGF resulted in dramatically reduced (6- fold) hepatic mRNA expression of pro-inflammatory cytokines IL-6, TNFα and MCP1 in the acute CCl4 model.