Moreover, Trpv1 depletion markedly blunted EtOH-me-diated induction of plasminogen activator inhibitor-1

(Pai-1), an important mediator of alcohol-induced hepatic inflammation, via fibrin accumulation. EtOH-induced DMXAA in vitro Pai-1 up-regulation in WT but not in Trpv1−/− animals was in parallel with the activation of hepatic ERK. Exposure of hepatocytes to 9-HODE and 13-HODE in vitro resulted in activation of TRPV1 signal trans-duction with increased intracellular Ca2+ levels, suggesting that OXLAM/TRPV1/Ca2+ signaling may be a potentially relevant pathway contributing to ALD. Conclusions: This study indicates for the first time that the TRPV1 receptor pathway may be involved in the hepatic inflammatory response in an experimental animal model of ALD. TRPV1-OXLAM interactions appear to play a significant role in hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD. Disclosures: Craig J. McClain – Consulting:

Vertex, Gilead, Baxter, Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing to disclose: Irina Kirpich, Keith C. Falkner, Juliane http://www.selleckchem.com/products/BIBW2992.html I. Beier, Gavin E. Arteel, Christopher Ramsden, Ariel E. Feldstein Background/Aim: Steatosis is an early pathogenic lesion in the spectrum of alcoholic liver disease. Neuropilin-1 (NRP) is a growth factor co-receptor implicated in hepatic stellate cell (HSC) activation. Recent studies have suggested that HSC may regulate parenchymal cell injury and inflammation that precedes liver fibrosis. Therefore, we sought to test the hypothesis that NRP in HSC may regulate steatosis in response to alcohol feeding in mice. Methods: NRP floxed mice (NRP-1loxP) were crossed with Collagen 1a Cre mice (ColCre) to generate mice with HSC selective deletion of NRP (ColCre/NRPloxP). Col-Cre/NRPloxP or pairfed wildtype mice were fed control or Lieber-deCarli diet for 10 days followed by alcohol

gavage (chronic/binge alcohol feeding model). Steatosis was measured and quantified by Oil Red staining, BODIPY staining, and triglyceride measurements from frozen liver tissues. Inflammation was assessed by real-time PCR for tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta) mRNA from liver 上海皓元 lysates. Results: Hepatic steatosis was 90% lower in ColCre/NRPloxP mice in response to alcohol feeding compared to wildtype animals (n=5-7; p<0.05) as assessed by Oil Red staining. This finding was confirmed by BODIPY staining (n=6-10; p<0.05). ColCre/NRPloxP mice also demonstrated a 50% reduction in hepatic triglyceride content after alcohol feeding compared to wildtype controls (p<0.05). TNF-alpha and IL-1beta mRNA expression increased 2 and 3 fold, respectively, in wild-type mice in response to alcohol feeding but not in ColCre/NRPloxP mice (n=6-10; p<0.05).