human, Cynomolgus/ Rhesus macaque, rat, mouse single immunoglobulin and toll-interleukin 1 receptor (TIR) domain (SIGIRR) for cell curture,in vitro study, in vivo study,benchmark, drug discovery & MOA research and positive control for the diagnosis.

Genemedi produces human, Cynomolgus/ Rhesus macaque, rat, mouse single immunoglobulin and toll-interleukin 1 receptor (TIR) domain (SIGIRR) His+Avi (Biotinylated) for cell curture, in vitro study, in vivo study, benchmark, drug discovery & MOA research and positive control for the diagnosis. Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate inflammation, immune response, and tumorigenesis of colonic epithelial cells. SIGIRR negatively regulates the activation of the IL-1R1, IL18R1, IL-1R5/ST2, TLR4, TLR7, TLR3, TLR9, and TLR1/2 and inhibits activation of transcription factor NF-κB and JNK MAP kinase. SIGIRR interacts with IL-1R1 when it binds IL-1. N terminal extracellular immunoglobulin domain associates with IL-1R1 and blocks its heterodimerization with IL-1RAP. In addition, C terminal TIR domain of SIGIRR binds downstream elements of IL-1R1 signalization and prevents the constitution of the functional signalling complex. Deletion of these domains disrupts the regulation activity of SIGIRR. SIGIRR uses a slightly different mechanism to regulate the activity of TLR4. It also binds to receptor complex around TLR4. TIR domain of SIGIRR is crucial for interaction with TLR4, and it also interacts with downstream elements of the TLR4 pathway. In contrast, the extracellular immunoglobulin domain of SIGIRR is dispensable for the inhibition of TLR4 signalling. There are 2 mechanisms, which are proposed for explanation of this inhibition of the TLR4 pathway. First is that SIGIRR blocks the formation of signalling complex at activated TLR4 and the second is that SIGIRR prevents translocation of this signalization complex into a cytosol. SIGIRR inhibits signal transduction by its interaction with TLRs, IL-1R1 and downstream signalling proteins, and in this manner, it participates in negative regulation of inflammation. SIGIRR also prevents homodimerization of MYD88, and it also prevents signalization through adaptor protein TRIF, which is used, for example, by TLR3.