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show by flow cytometry analysis, western blot, confocal microscopy, and quantitative real-time polymerase chain reaction that IL-1R8 is expressed (zeige IL1RAPL1 Proteine) 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 (zeige IRF6 Proteine) 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 (zeige CD4 Proteine)+ 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 acts as an extracellular cytokine by binding to the IL-18 (zeige IL18 Proteine) receptor but using the IL-1R8 for its anti-inflammatory properties.
Lipopolysaccharide decreases SIGIRR expression by suppressing specificity protein 1 Sp1 (zeige SP1 Proteine) via the TLR4 (zeige TLR4 Proteine)-p38 (zeige CRK Proteine) pathway in monocytes and neutrophils.
Here the authors show that hyperactivation of the interleukin 1 pathway, through either ablation of the interleukin 1 receptor 8 (IL-1R8, also known as SIGIRR or Tir8) or activation of IL-1R, leads to up-regulation of the mTOR pathway and increased levels of the epigenetic regulator MeCP2, bringing to disruption of dendritic spine morphology, synaptic plasticity and plasticity-related gene expression.
Commensal flora depletion and IL-1R1 deficiency abated platelet hyperactivity and the increased platelet/neutrophil aggregation observed in Il1r8 (zeige IL1RAPL1 Proteine)(-/-) mice in vitro and in vivo, suggesting a key role of IL-1R8 in regulating platelet TLR and IL-1R1 function
Expression of SIGIRR(N86/102S) in the colonic epithelium of mice increases expression of inflammatory cytokines and formation and size of colitis-associated tumors.
IL-37 requires IL-18Ralpha and SIGIRR/IL-1R8 to diminish allergic airway inflammation in mice
Thus, SIGIRR expression by IEC reflects a strategy that sacrifices maximal innate responsiveness by IEC in order to promote commensal microbe based colonization resistance against bacterial pathogens.
This study identifies TIR8/SIGIRR as a novel intrinsic negative regulator of innate IL-17A (zeige IL17A Proteine) expression
Absence of TIR8 reduces house dust mite-induced allergic airway inflammation in mice.
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