title: SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.
abstract: The Toll-like receptor-interleukin 1 receptor signaling (TLR-IL-1R) receptor superfamily is important in differentially recognizing pathogen products and eliciting appropriate immune responses. These receptors alter gene expression, mainly through the activation of nuclear factor-kappaB and activating protein 1. SIGIRR (single immunoglobulin IL-1R-related molecule), a member of this family that does not activate these factors, instead negatively modulates immune responses. Inflammation is enhanced in SIGIRR-deficient mice, as shown by their enhanced chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. Cells from SIGIRR-deficient mice showed enhanced activation in response to either IL-1 or certain Toll ligands. Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling.
authors.affiliation: Cleveland Clinic Foundation, Department of Immunology, Cleveland, Ohio 44195, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wald
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Qin
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Youcun
authors.initials: Y
authors.lastname: Qian
authors.forename: Mayumi
authors.initials: M
authors.lastname: Naramura
authors.forename: Liping
authors.initials: L
authors.lastname: Tian
authors.forename: Jennifer
authors.initials: J
authors.lastname: Towne
authors.forename: John E
authors.initials: JE
authors.lastname: Sims
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1 / Q000276:immunology
chemical_list: D018925:Chemokines; D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D012313:RNA