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1: Nat Immunol. 2003 Sep;4(9):920-7. Epub 2003 Aug 17.Click here to read Links
Comment in:
Nat Immunol. 2003 Sep;4(9):823-4.

SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.

Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X.

Cleveland Clinic Foundation, Department of Immunology, Cleveland, Ohio 44195, USA.

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.

PMID: 12925853 [PubMed - indexed for MEDLINE]