toll-like receptors in the pathogenesis of alcoholic liver diseasetoll样受体在酒精性肝病的发病机制.pdfVIP

Hindawi Publishing Corporation Gastroenterology Research and Practice Volume 2010, Article ID 710381, 12 pages doi:10.1155/2010/710381 Review Article Toll-Like Receptors in the Pathogenesis of Alcoholic Liver Disease Jan Petrasek, Pranoti Mandrekar, and Gyongyi Szabo Department of Medicine, University of Massachusetts Medical School, LRB215, 364 Plantation Street, Worcester, MA 01605, USA Correspondence should be addressed to Gyongyi Szabo, gyongyi.szabo@ Received 20 May 2010; Accepted 20 July 2010 Academic Editor: Keigo Machida Copyright © 2010 Jan Petrasek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the multifactorial pathophysiology of alcoholic liver disease (ALD), inflammatory cascade activation plays a central role. Recent studies demonstrated that Toll-like Receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD. In this paper, we discuss the importance of gut-derived endotoxin and its recognition by TLR4. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of reactive oxygen radicals is evaluated. The contribution of TLR signaling to induction of liver fibrosis and hepatocellular cancer is reviewed in the context of alcohol-induced liver disease. 1. Introduction the liver sinusoids not only to nutrients but also to gut- derived microbial products. The gut mucosal epitheli