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Description: IL-27, a member of the IL-12 family, is a heterodimeric protein consisting of the p40-related protein Epstein-Barr virus-induced gene 3 (EBI3) non-covalently linked to an IL-12p35-related protein, p28 (also known as IL-30). IL-27 is produced by activated APCs and mature dendritic cells. IL-27 exerts its activities on NK cells and naive CD4+ T cells; mRNA expression analysis of IL-27 receptor components (WSX-1/TCCR and gp130) suggests that IL-27 may also target other cells, including mast cells and monocytes. Binding of IL-27 to WSX-1/gp130 activates JAK1, STAT1, and STAT3 and STAT1/3 phosphorylation. WSX-1/TCCR-deficient mice develop impaired Th1 responses and are more susceptible to infection with L. monocytogenes suggesting that Th1 responses require IL-27. Although activation of WSX-1 is required for the initiation of Th1 responses, it is not necessary for maintaining Th1 responses. IL-27 alone is not able to induce the differentiation of CD4+ T cells into IFN-gamma-producing cells, suggesting a role for IL-27 as an initial activator of Th1 responses. An important effect of IL-27 in initiating Th1 responses is the induction of the Th1-specific transcription factor T-bet as well as the suppression of the Th2-specific transcription factor GATA-3. T-bet plays a critical role in Th1 differentiation by its ability to maintain IL-12Rbeta2 expression following CD4+ T cell activation.
Recent studies indicate that IL-27 has a potent antitumor activity. In vitro, IL-27 has been found to act directly on naive CD8 cells, generating CTL with enhanced granzyme B expression. In vivo, IL-27 has been reported to augment CTL activity, inhibit tumor growth, and induce complete regression of primary and metastatic neuroblastoma tumors.
Applications Reported: The recombinant mouse IL-27 (EBI3/p28) has been reported useful for bioassay.
Applications Tested: This recombinant mouse IL-27 (EBI3/p28) has been tested in bioassay for inhibition of IL-2 production by mouse splenocytes activated with immobilized anti-CD3 and soluble anti-CD28 antibodies (Villarino, A.V., et al. 2006. J. Immunol. 176: 237). The ED50 for this is typically 50 ng/mL, corresponding to a specific activity of 2.0 x 10e4 Units/mg.
Source: Mouse EBI3 met 1-pro 228; accession # BC008209 linked through a gly-gly-gly-gly-Ser3 to mature P28/IL-30 phe 29-Ser 234; accession # NM_145636 tagged at the C-terminal with thr-gly-his10 was expressed in human 293 cells.
Bioactivity: Measured in a bioassay of IL-27-mediated inhibition of IL-2 production by mouse splenocytes activated with immobilized anti-CD3 and soluble anti-CD28 antibodies (Villarino, A.V., et al. 2006. J. Immunol. 176: 237). The ED50 for this is typically 50 ng/mL, corresponding to a specific activity of 2.0 x 10e4 U/mg.
Endotoxin: Less than 0.01 ng/ug cytokine as determined by the LAL assay. Purity: >98% as determined by SDS-PAGE.
Molecular Weight: After removal of the secretion signal the mature EBI3-linker-mature P28-His10 protein has a predicted molecular mass of approximately 49,000. On non-reducing and reducing SDS-PAGE the linked protein migrates as a 55 kDa protein due to glycosylation.
Storage and handling: For best recovery, quick-spin vial prior to opening. Use in a sterile environment.
IL-27 (Interleukin 27) is a cytokine belonging to the IL-12 family, and is a heterodimeric cytokine composed of EBI3 and p28 subunits. IL-27 is produced by activated dendritic cells and macrophages in response to Toll-like receptor ligands and pro-inflammatory cytokines. IL-27 promotes CD4+ T cell differentiation to the Th1 lineage by inducing expression of the transcription factor T-bet and up regulating IL-12R beta2, which in turn suppresses Th2 and Th17 differentiation and proliferation. IL-27 is a recently discovered member of the IL-6/IL-12 family of proinflammatory and immunoregulatory cytokines. IL-27 acts by binding to its receptor WSX-1 and gp130 which results in the activation of a Jak/STAT signaling cascade, suggesting IL-27 involvement in the regulation of immune processes. It has been suggested that IL-27 can also be used as a therapeutic agent against cancer as it can also induce tumor-specific anti-tumor activity mediated through CD8+ T-cells, IFN-gamma, and T-bet. In humans, the gene is located on the p arm of chromosome 16.
For Research Use Only. Not for use in diagnostic procedures. Not for resale without express authorization.
Protein Aliases: Epstein-Barr virus-induced gene 3 protein homolog; IL-27 p28 subunit; IL-27 subunit alpha; IL-27 subunit beta; IL-27-A; IL-27B; IL27 p28; IL27-A; ILN; Interleukin; interleukin 30; Interleukin-27 subunit alpha; Interleukin-27 subunit beta; M-IL-27 (p28); MGC71873; p28
Gene Aliases: Ebi3; Il27; Il27a; Il27b
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