Open AccessNegative regulation of Toll-like receptor signalling
Author(s) -
H Antosz,
Dorota Choroszyńska
Publication year - 2013
Publication title -
postępy higieny i medycyny doświadczalnej
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.275
H-Index - 34
eISSN - 1732-2693
pISSN - 0032-5449
DOI - 10.5604/17322693.1046538
Subject(s) - trif , microbiology and biotechnology , signal transducing adaptor protein , proinflammatory cytokine , receptor , pattern recognition receptor , innate immune system , signal transduction , intracellular , transcription factor , biology , chemokine , iκb kinase , toll like receptor , nf κb , inflammation , immunology , biochemistry , gene
The mechanism of innate immunity is based on the pattern recognition receptors (PRR) that recognize molecular patterns associated with pathogens (PAMPs). Among PRR receptors Toll-like receptors (TLR) are distinguished. As a result of contact with pathogens, TLRs activate specific intracellular signaling pathways. It happens through proteins such as adaptor molecules, e.g. MyD88, TIRAP, TRIF, TRAM, and IPS-1, which participate in the cascade activation of kinases (IKK, MAP, RIP-1, TBK-1) as well as transcription factors (NF-κB, AP-1) and regulatory factor (IRF3). The result of this activation is the production of active proinflammatory cytokines, chemokines, interferons and enzymes. The PRR pathways are controlled by extra- and intracellular molecules to prevent overexpression of PRR. They include soluble receptors (sTLR), transmembrane proteins (ST2, SIGIRR, RP105, TRAIL-R) and intracellular inhibitors (SOCS-1, SOCS-3, sMyD88, TOLLIP, IRAK-M, SARM, A20, β-arrestin, CYLD, SHP). These molecules maintain the balance between activation and inhibition and ensure balancing of the beneficial and adverse effects of antigen recognition.