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Toll‐like receptors and adaptor molecules in liver disease: Update
Author(s) -
Seki Ekihiro,
Brenner David A.
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22306
Subject(s) - trif , signal transducing adaptor protein , biology , microbiology and biotechnology , receptor , toll like receptor , innate immune system , pattern recognition receptor , signal transduction , immunology , immune system , biochemistry
Toll‐like receptors (TLRs) are pattern recognition receptors that recognize pathogen‐associated molecular patterns and signal through adaptor molecules, myeloid differentiation factor 88 (MyD88), Toll/IL‐1 receptor domain containing adaptor protein (TIRAP), Toll/IL‐1 receptor domain containing adaptor inducing interferon‐β (TRIF), and TRIF‐related adaptor molecule (TRAM) to activate transcription factors, nuclear factor (NF)‐κB, activator protein 1 (AP‐1), and interferon regulatory factors (IRFs) leading to the initiation of innate immunity. This system promptly initiates host defenses against invading microorganisms. Endogenous TLR ligands such as the products from dying cells may also engage with TLRs as damage‐associated molecular patterns. Although Kupffer cells are considered the primary cells to respond to pathogen associated molecular patterns in the liver, recent studies provide evidence of TLR signaling in hepatic nonimmune cell populations, including hepatocytes, biliary epithelial cells, endothelial cells, and hepatic stellate cells. This review highlights advances in TLR signaling in the liver, the role of TLRs in the individual hepatic cell populations, and the implication of TLR signaling in acute and chronic liver diseases. We further discuss recent advances regarding cytosolic pattern recognition receptors, RNA helicases that represents a new concept in chronic hepatitis C virus infection. (H EPATOLOGY 2008.)