SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.
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.
Mesh Terms:
Animals, Chemokines, Gene Expression Regulation, Humans, Immunoblotting, Interleukin-1, Interleukin-18, Jurkat Cells, Lipopolysaccharides, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, RNA, Receptors, Cell Surface, Receptors, Interleukin-1, Signal Transduction, Toll-Like Receptors, Transcription Factor AP-1
Animals, Chemokines, Gene Expression Regulation, Humans, Immunoblotting, Interleukin-1, Interleukin-18, Jurkat Cells, Lipopolysaccharides, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, RNA, Receptors, Cell Surface, Receptors, Interleukin-1, Signal Transduction, Toll-Like Receptors, Transcription Factor AP-1
Nat. Immunol.
Date: Sep. 01, 2003
PubMed ID: 12925853
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