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SIGIRR is both a negative regulator of TLR4 and a positive regulator of TLR7/8.
Our results indicate that high IL-1R8 expression acts as a novel immunomodulatory mechanism leading to dysregulated immunity with important implications for breast cancer immunotherapy.
show by flow cytometry analysis, western blot, confocal microscopy, and quantitative real-time polymerase chain reaction that IL-1R8 is expressed on human and mouse platelets at high levels and on megakaryocytes. IL-1R8-deficient mice show normal levels of circulating platelets
Tir8/SIGIRR acts anti-inflammatory on different immune responses,its function in allergic asthma is a controversial issue, since anti- as well as pro-inflammatory effects have been reported
SIGIRR plays an important role in the negative regulation of LPS response and tolerance in human bladder epithelial cells, possibly through its impact on TLR-mediated signaling.
Levels of SIGIRR are lower in human colorectal tumors, compared with nontumor tissues; tumors contain the dominant-negative isoform SIGIRR(DeltaE8).
SIGIRR predicts biochemical recurrence in patients with low Gleason score and low pathological stage prostate cancer.
decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR may be involved in the pathogenesis of SLE.
To the best of our knowledge, this is one of the first reports of a phenotype associated with SIGIRR in humans. Our data provide novel mechanistic insight into the probable causation of necrotizing enterocolitis
An association was found in the SIGIRR rs7396562 polymorphism and systemic lupus erythematosus susceptibility in a Chinese population.
IL-37 requires the receptors IL-18Ralpha and IL-1R8 to carry out its multifaceted anti-inflammatory program upon innate signal transduction.
IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor but using the IL-1R8 for its anti-inflammatory properties.
Lipopolysaccharide decreases SIGIRR expression by suppressing specificity protein 1 Sp1 via the TLR4-p38 pathway in monocytes and neutrophils.
The present study was undertaken to characterize responses of B cells from systemic lupus erythematosus patients to TLR7 and TLR9 stimulation and to explore the potential role of SIGIRR.
the tested variations of IRAK-M and SIGIRR genes do not confer a relevant role in the susceptibility to systemic lupus erythematosus in European-descent populations
These results demonstrate a strong association of single-nucleotide polymorphisms in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts.
SIGIRR can inhibit TLR4, 5, and 9-mediated immune responses in human airway epithelial cells.
These results suggest that PALM3 may function as an adaptor in the LPS- Toll-like receptor 4 signaling and the interaction of SIGIRR with PALM3 may partly account for the mechanism of the negatively regulatory effect of SIGIRR.
SIGIRR is expressed constitutively in intestinal epithelial cells to maintain gut innate immunity and then down-regulated during inflammation by inhibition of an SP1-mediated pathway.
SIGIRR/TIR-8 is an inhibitor of Toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritis
this study is the first to report a functional SIGIRR homolog that existed in a lower vertebrate; this molecule is essential to establish liver homeostasis under inflammatory stimuli
TIR8 was found in the GI tract and kidney. Expression of TIR8 mRNA was detected in lymph nodes, thymus and thyroid gland. Several isoforms of TIR8 were detected in the same organs, suggesting the occurrence of different post-translational processings.
Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP (By similarity).
single Ig IL-1-related receptor
, single Ig IL-1R-related molecule
, single immunoglobulin domain IL1R1 related
, single immunoglobulin domain-containing IL1R-related protein
, toll/interleukin-1 receptor 8
, single Ig IL-1 receptor related protein
, single Ig IL-1R-related protein