Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses.
Toll-like receptors (TLRs) have a crucial role in regulating immunity against microbial agents. Recent studies indicate that these receptors might also have an important role in regulating responses to endogenous stimuli, such as necrotic cells, heat-shock proteins and extracellular matrix breakdown products. Specifically, TLR2 and TLR4 were shown to mediate expression of inflammatory genes and trigger dendritic-cell 'maturation' by these agents. These intriguing findings suggest that the ancient family of TLRs are involved in the recognition, not only of microbes, but also of endogenous harmful stimuli. However, potential complications associated with microbial contamination of endogenous agents and the specific nature of in vivo responses induced by these agents remain to be determined.
Beg
Amer A
AA
Dept of Biological Sciences, 1110 Fairchild Center, 1212 Amsterdam Ave, Columbia University, New York, NY 10027, USA. aab41@columbia.edu
D000818:Animals; D016923:Cell Death; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors