toll-like receptor signaling and liver fibrosistoll样受体信号和肝纤维化.pdfVIP

Hindawi Publishing Corporation Gastroenterology Research and Practice Volume 2010, Article ID 192543, 8 pages doi:10.1155/2010/192543 Review Article Toll-Like Receptor Signaling and Liver Fibrosis Tomonori Aoyama,1 Yong-Han Paik,1, 2 and Ekihiro Seki1 1 Division 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 2 Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 135-720, Republic of Korea Correspondence should be addressed to Ekihiro Seki, ekseki@ 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. 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