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Fig. 5. Toll-like receptor (TLR) signalling involves JNK and NF-κB p65 activation. Toll-like receptors (TLR) constitute a family of receptors involved in pro-inflammatory signalling in the innate immune system, responsible for the recognition of pathogen-associated molecular patterns (PAMPs) and exogenous stimuli, such as pathogens, or endogenous agonists, such as sterile tissue damage; the later are termed danger-associated molecular patterns (DAMPs). Of the 9 known TLR receptors, four (TLR-3, -7, -8, and -9) are expressed on the endosomal membrane and are responsible for viral particle surveillance, including detection of deoxy-cytidylate-phosphate-deoxy-guanylate DNA (CpG-DNA), and single- and double-stranded RNA. The remaining TLRs are expressed on the plasma membrane and are responsible for the detection of extracellular microbial pathogens. Relevant PAMPs include: LPS, diacyl- and triacyl lipopeptides, and flagellin, as well as several DAMPs, including HMGB1. Activated TLR3, as well as TLR4, signal through adaptor protein TIR-domain-containing adapter-inducing interferon-β (TRIF), which in turn recruits RIP1 to activate the IKK complex, thereby activating nuclear factor-kappa B (NF-κB). The other TLRs signal through toll/interleukin-1 receptor domain containing adaptor protein (TIRAP) and myeloid differentiation factor 88 (Myd88). Activated Myd88 induces the recruitment of IL-1R-associated kinase (IRAK) 4, as well as IRAK1, which bind TRAF-6 and transforming growth factor-β activated kinase (TAK)-1. IRF5 and IRF7 are then recruited to the post-Myd88 protein complex. Interferon-regulatory factor 7 (IRF7) recruitment is dependent upon on TLR7 and TLR9 signalling. The IRAK1/4/TRAF6/TAK1/IRF5/7 complex is responsible for downstream Myd88-dependent activation of c-Jun N-terminal kinase (JNK) and NF-κB. TRAF, tumor necrosis factor (TNF) receptor-associated factor; MEKK, MAP kinase kinase kinase; MKK, mitogen-activated protein kinase kinase; ASK, apoptosis signal-regulating kinase.
Gut Liver 2012;6:149~171 https://doi.org/10.5009/gnl.2012.6.2.149
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