Original Literature | Model OverView |
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Publication
Title
Regulatory pathways in inflammation.
Affiliation
Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy.alberto.mantovani@humanitas.it
Abstract
Tuning is a key aspect of inflammatory reaction essential in homeostasis andpathology. An emerging mechanism for negative regulation of proinflammatorycytokines is based on non-signaling IL-1/TLR receptors and chemokine receptorscompeting with signaling receptors for ligand binding and sustaining ligandinternalization and degradation. Biological activities of IL-1R/TLR receptorsare under control of membrane-bound binding molecules lacking the signalingdomain, soluble receptor antagonists, and intracellular signaling inhibitors.The chemokine system includes at least three 'silent' receptors with distinctspecificity and tissue distribution. D6 is the best characterized representativemember of this class of negative regulators, binds most inflammatory, but nothomeostatic, CC chemokines and shuttles in a ligand-independent way from theplasma membrane to endocytic compartments where chemokines are targeted todegradation. In vitro and in vivo evidence, including results with gene targetedmice, is consistent with the view that these non-signaling receptors forproinflammatory cytokines possess unique functional and structural featureswhich make them ideally adapted to act as a decoy and scavenger receptors, witha non redundant role in dampening tissue inflammation and tuning draining lymphnodes reactivity.
PMID
17967718
|
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PMID: 17967718 IL-1RII, which lacks a signaling domain, both in membrane-bound or released form, binds IL-1 preventing its interaction with a signaling receptor complex
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PMID: 17967718 IL-1RII, which lacks a signaling domain, both in membrane-bound or released form, binds IL-1 preventing its interaction with a signaling receptor complex
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PMID: 17967718 IL-1RII, which lacks a signaling domain, both in membrane-bound or released form, binds IL-1 preventing its interaction with a signaling receptor complex
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PMID: 17967718, 8332913, 7848516, 11377293 In addition, it forms a dominant negative non signaling complex with the accessory protein (AcP)
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PMID: 17967718 D6 binds a broad range of ligands that includes most of the inflammatory CC chemokines
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PMID: 17967718, 15308102, 12538665 A negative regulation of signal transduction is exerted by IRAK-M, one of the members of the IL-1 receptor associated kinase (IRAK) family, which lacks kinase activity and regulates the dissociation of IRAK-1 and IRAK-4 from the adaptor protein MyD88, and by MyD88s a spliced form of MyD88 which prevents IRAK-4 recruitment.
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PMID: 17967718, 15308102, 12538665 A negative regulation of signal transduction is exerted by IRAK-M, one of the members of the IL-1 receptor associated kinase (IRAK) family, which lacks kinase activity and regulates the dissociation of IRAK-1 and IRAK-4 from the adaptor protein MyD88, and by MyD88s a spliced form of MyD88 which prevents IRAK-4 recruitment.
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PMID: 17967718, 15308102, 12538665 A negative regulation of signal transduction is exerted by IRAK-M, one of the members of the IL-1 receptor associated kinase (IRAK) family, which lacks kinase activity and regulates the dissociation of IRAK-1 and IRAK-4 from the adaptor protein MyD88, and by MyD88s a spliced form of MyD88 which prevents IRAK-4 recruitment.
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PMID: 17967718, 15308102, 12538665 A negative regulation of signal transduction is exerted by IRAK-M, one of the members of the IL-1 receptor associated kinase (IRAK) family, which lacks kinase activity and regulates the dissociation of IRAK-1 and IRAK-4 from the adaptor protein MyD88, and by MyD88s a spliced form of MyD88 which prevents IRAK-4 recruitment.
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