BCL2L1, BLVRA, CCND1, CCND2, CCND3, CD14, CDKN2D, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL1B, IL6, JAK1, MAP2K6, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MYC, NFKB1, NFKB2, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R3, PIM1, REL, RELA, RELB, SOCS3, STAT3, TIA1, TLR4, TNF, TYK2
IL-10 (Interleukin-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. It is a cytokine with potent anti-inflammatory properties, repressing the express ...ion of inflammatory cytokines such as TNF-Alpha (Tumor Necrosis Factor-Alpha), IL-6 (Interleukin-6) and IL-1 (Interleukin-1) by activated macrophages. Functional IL-10R (IL-10 Receptor) complexes are tetramers consisting of two ligand-binding subunits (IL-10R-Alpha or IL-10R1) and two accessory signaling subunits (IL-10R-Beta or IL-10R2). Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated, JAK1 (Janus Kinase-1) and TYK2 (Tyrosine Kinase-2), which are constitutively associated with IL-10R1 and IL-10R2, respectively. These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. Once phosphorylated these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (Signal Transducer and Activator of Transcription-3). STAT3 binds to these sites via its SH2 (Src Homology-2) domain, and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs. It then homodimerizes and translocates to the nucleus where it binds with high affinity to SBE (STAT-Binding Elements) in the promoters of various IL-10-responsive genes. Constitutively active forms of STAT3 increase transcription of anti-apoptotic and cell-cycle-progression genes such as BCLXL, Cyclin-D1, Cyclin-D2, Cyclin-D3, Pim1, c-Myc and p19 (INK4D). IL-10 has also been reported to activate another major survival pathway consisting of PI3K (Phosphoinositide-3 Kinase).Although the anti-inflammatory effects of IL-10 are not mediated via PI3K, the ability of IL-10 to promote survival of astrocytes or to induce proliferation of mast cells depends upon the activation of PI3K. IL-10 also interferes with the activation potential of the p38MAPK (Mitogen-Activated Protein Kinase) pathway, which is required to activate TNF (Tumor Necrosis Factor) translation.
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Supported Applied Biosystems Instruments
7500 Fast Real-Time PCR System
,
StepOnePlus™ System
,
ViiA™ 7 System
,
7900HT Real-Time PCR System
,
QuantStudio™ 12K Flex System
,
QuantStudio™ 7 Flex System
,
QuantStudio™ 6 Flex System
,
QuantStudio™ 5 System
,
QuantStudio™ 3 System