Regulation of TLR by endogenous ligand

Stable Identifier
R-HSA-5686938
Type
Pathway
Species
Homo sapiens
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Summation

Diverse molecules of host-cell origin may serve as endogenous ligands of Toll-like receptors (TLRs) (Erridge C 2010; Piccinini AM & Midwood KS 2010). These molecules are known as damage-associated molecular patterns (DAMPs). DAMPs are immunologically silent in healthy tissues but become active upon tissue damage during both infectious and sterile insult. DAMPs are released from necrotic cells or secreted from activated cells in response to tissue damage to mediate tissue repair by promoting inflammatory responses. However, DAMPs have also been implicated in the pathogenesis of many inflammatory and autoimmune diseases, including rheumatoid arthritis (RA), cancer, and atherosclerosis. The mechanism underlying the switch from DAMPs that initiate controlled tissue repair, to those that mediate chronic, uncontrolled inflammation is still unclear. Recent evidence suggests that an abnormal increase in protein citrullination is involved in disease pathophysiology (Anzilotti C et al. 2010; Sanchez-Pernaute O et al. 2013; Sokolove J et al. 2011; Sharma P et al. 2012). Citrullination is a post-translational modification event mediated by peptidyl-arginine deaminase enzymes which catalyze the deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions.

Literature References
PubMed ID Title Journal Year
25391648 Complexity of danger: the diverse nature of damage-associated molecular patterns

Schaefer, L

J. Biol. Chem. 2014
20179153 Endogenous ligands of TLR2 and TLR4: agonists or assistants?

Erridge, C

J. Leukoc. Biol. 2010
20629986 Endogenous toll-like receptor ligands and their biological significance

Yu, L, Wang, L, Chen, S

J. Cell. Mol. Med. 2010
20706656 DAMPening inflammation by modulating TLR signalling

Piccinini, AM, Midwood, KS

Mediators Inflamm. 2010
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