BACKGROUND Interleukin (IL)-23, belongs to the growing family of IL-12 related cytokines which also including IL-27, is a heterodimeric cytokine with many similarities to IL-12, has recently been identified as a factor linking tumor-associated inflammation and a lack of tumor immune surveillance. IL-23 comprises a p19 subunit that associates with the IL-12p40 subunit, whereas IL-12 is a combination of IL-12p35 and the same IL-12p40 subunit. Furthermore, IL-23p19 is a molecule structurally related to not only IL-6, but also granulocyte-colony stimulating factor (G-CSF), and the p35 subunit of IL-12. Although p19 is expressed in various tissues and cell types, it lacks biological activity and only becomes biologically active when complexed with p40, which is normally secreted by activated macrophages and dendritic cells (DCs). IL-23 uses many of the same signal-transduction components as IL-12, including the IL-12 receptor (R) ß1 subunit (IL-12Rß1), Janus kinase (Jak)2, Tyk2, signal transducer and activator of transcription (Stat)1, Stat3, Stat4, and Stat5. IL-23R, composed of the IL-12Rß1 and the IL-23R subunit, is also expressed in DCs, macrophages, and T cells. Consistent with the structural and biological similarities of IL-12 and IL-23, the IL-23R complex shares a subunit with that of IL-12 (IL-12Rß1); however, it does not use or detectably bind to IL-12Rß2. The ability of cells to respond to either IL-12 or IL-23 is determined by expression of IL-12Rß2 or IL-23R, respectively. Additionally, both cytokines promote the T helper cell type 1 (Th1) costimulatory function of antigen-presenting cells. However, IL-23 does differ from IL-12 in the T cell subsets that it targets. IL-12 acts on naive CD4+ T cells, whereas IL-23 preferentially acts on memory CD4+ T cells. Mouse memory T-cells (CD4(+) CD45 Rb(low)) proliferate in response to IL23 but not in response to IL12.1
It has been reported that IL-12 has potent antitumor activity in a variety of murine tumor models, causing regression of established tumors and inhibiting the formation of experimental metastases and spontaneous metastases. On the other hand, it has recently been reported that genetic deletion or antibody-mediated elimination of IL-23 in mice leads to increased infiltration of cytotoxic T cells into the transformed tissue, rendering a protective effect against chemically-induced carcinogenesis. So far, it has been reported that expression of IL-23 and its receptors is detectable in activated macrophages, DCs, and keratinocytes in healthy skin. It was also demonstrated that the human oral squamous cell carcinoma (HOSCC) cell line, HSC-3, spontaneously expresses IL-23 and its receptors mRNA and protein. IL-23 up-regulates the growth and cell proliferation of oral cancer by promoting the nuclear transactivation of RelA.2 Human IL23 has been shown to stimulate the production of IFN-gamma by PHA blast T-cells and memory T-cells. It also induces proliferation of both cell types. Human monocyte-derive macrophages produce IL23 in response to virus infection (Sendai virus but not Influenza A virus). Expression of p19 in transgenic mice leads to runting, systemic inflammation, infertility, and death before 3 months of age. The animals show high serum concentrations of the pro-inflammatory cytokines TNF-alpha and IL1. The number of circulating neutrophils is increased. Acute phase proteins are expressed constitutively. It was also shown that IL23 plays a prominent role in the regulation of granulopoiesis and the prevalence of neutrophil-regulatory T-cells.3
1. Yen, D. et al: J. Clin. Invest. 116:1310–16, 2006
2. Fukuda, M. et al: Int. J. Oncol. 36:1355-65, 2010
3. Smith, E. et al: J. Immunol. 179:8274-9, 2007
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Target Protein Species:
No detectable cross-reactivity
with any other cytokine.
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ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.