Toll-like receptor signalling pathways as key targets for mediating the anti-inflammatory and immunosuppressive effects of glucocorticoids.
Toll-like receptors (TLRs) play crucial roles in the induction of innate immune responses by recognising pathogen-associated molecular patterns. The engagement of TLRs by pathogens results in induction of co-stimulatory molecules that facilitate a specific immune response and also in the induction of pro-inflammatory proteins that will promote the elimination of pathogens from the body. TLRs employ many of the same signalling components as the type I interleukin (IL)-1 receptor (IL-1R). This is hardly surprising since the intracellular regions of TLRs and the IL-1R share a conserved Toll/IL-1R homology domain (TIR) that allows the receptors to recruit the intracellular TIR-containing adaptor protein Myd88. The latter then activates IL-1R-associated kinases that in turn recruit well-characterised downstream effectors culminating in activation of MAP kinases and transcription factors such as NFkappaB and AP-1. Since glucocorticoids are known to target the latter transcription factors and the MAP kinase cascades, this commentary highlights the likely crucial importance of Toll-like receptor signalling pathways as key targets for mediating the anti-inflammatory and immunosuppressive effects of steroids.
Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. P.Moynagh@ucd.ie
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D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors