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Gastroenterology Research and Practice
Volume 2010, Article ID 192543, 8 pages
http://dx.doi.org/10.1155/2010/192543
Review Article

Toll-Like Receptor Signaling and Liver Fibrosis

1Division of Gastroenterology, Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive MC# 0702, Leichtag Biomedical Research Building Rm# 332 MM, La Jolla, CA 92093-0702, USA
2Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 135-720, Republic of Korea

Received 24 March 2010; Accepted 16 June 2010

Academic Editor: Ian Nicholas Crispe

Copyright © 2010 Tomonori Aoyama 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.

Abstract

Liver fibrosis occurs as a wound-healing scar response following acute and chronic liver inflammation including alcoholic liver disease, non-alcoholic steatohepatitis, hepatitis B and C, and autoimmune hepatitis. Myofibroblasts, mainly transdifferentiated from hepatic stellate cells, are pivotal cell types that produce fibrillar collagen. The activation of inflammatory cells, including Kupffer cells, is a crucial step for activating hepatic stellate cells. Toll-like receptors (TLRs) are pattern recognition receptors that sense pathogen-associated molecular patterns (PAMPs), which discriminate the products of microorganisms from the host. TLRs are expressed on Kupffer cells, endothelial cells, dendritic cells, biliary epithelial cells, hepatic stellate cells, and hepatocytes in the liver. TLR signaling induces potent innate immune responses in these cell types. The liver is constantly exposed to PAMPs, such as LPS and bacterial DNA through bacterial translocation because there is a unique anatomical link, the portal vein system between liver and intestine. Recent evidence demonstrates the role of TLRs in the activation of hepatic immune cells and stellate cells during liver fibrosis. Moreover, crosstalk between TLR4 signaling and TGF- signaling in hepatic stellate cells has been reported. This paper highlights the role of TLR signaling in stellate cell activation and the progression of liver fibrosis.