Description: The monoclonal antibody RN17 reacts with and inhibits the bioactivity of mouse IL-17F. IL-17F is a 37kD homodimer of the IL-17 family and a signature Th17 marker. Of all the six IL-17 family members, IL-17F and IL-17A share the strongest homology (50% amino acid identity), and the two genes are located in the same chromosomal region. Recent studies have demonstrated coordinated regulation of IL-17A and IL-17F during Th17 differentiation. Expression of IL-17F and IL-17A has been detected in activated human peripheral blood lymphocytes, specifically by activated human CD4^+ T cells. In addition to IL-17A, differentiated Th17 cells also produce IL-17F and IL-22 upon re-activation. Like IL-17A, IL-17F has been linked with inflammatory diseases. IL-17F and IL-17A expression has been observed in tissue samples from various autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, and asthma. IL-17F treatment of airway epithelium, vein endothelial cells, and fibroblasts has been reported to induce expression of IL-6, IL-8, GRO-alpha, ENA-78, TGF-beta, MCP-1, G-CSF, GM-CSF, and ICAM-1. Like IL-17A, IL-17F is a disulfide-linked homodimeric glycoprotein. The IL-17F homodimer includes a classical cysteine knot motif, which is found also in the TGF-beta, BMP, and NGF superfamilies.The presence of the cysteine knot motif suggested the possibility of a heterodimeric structure, as was reported for TGF-beta and inhibin/activin. Recent reports confirm that co-expression of IL-17F and IL-17A in HEK293 cells results in the formation of biologically active IL-17F/IL-17A heterodimers, in addition to the IL-17F homodimers and IL-17A homodimers. Moreover, activated human CD4^+ T cells were found to produce the IL-17A/F heterodimer, along with the corresponding homodimers. In comparing the relative potency of IL-17A, IL-17F, and IL-17A/F, all three were found to induce GRO-alpha secretion; IL-17A was most potent, followed by IL-17A/F heterodimer, then IL-17F (100fold lower than IL-17A). In the mouse, the IL-17A/F heterodimer (alone or in synergy with TNF-alpha) was found to regulate the expression of IL-6 and KC (mouse homolog of human GRO-alpha); this was found to be dependent on IL-17RA and TRAF6. Applications Reported: This monoclonal antibody reacts with and inhibits the bioactivity of mouse IL-17F. Applications Tested: The ND50 of RN17 as measured by the inhibition of mouse IL-6 induction in NIH/3T3 cells is 1-6 µg/mL in the presence of 4 µg/mL of recombit mouse IL-17F. Neutralization dose will vary depending on assay method, cytokine concentration, and cell type. This antibody should be carefully titrated for optimal performance in the assay of interest. Endotoxin: Less than 0.001 ng/ug antibody as determined by the LAL assay. Storage and handling: Use in a sterile environment. Filtration: 0.2 µm post-manufacturing filtered. Purity: Greater than90%, as determined by SDS-PAGE. Endotoxin Level: Less than 0.001 ng/µg antibody, as determined by LAL assay. Aggregation: Less than 10%, as determined by HPLC. IL-17F (Interleukin 17F, CTLA-8)) is a cytokine belonging to the IL-17 family that is produced by inflammatory cells such as activated T cells, mast cells, and basophils. IL-17F is involved in allergic airway inflammation, and can induce several cytokines, chemokines, and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts, and eosinophils. IL-17F may be secreted as a homodimer, or a heterodimer with IL17A. It acts by binding to the type I receptor, IL-17R, aiding recruitment of monocytes and neutrophils at the site of inflammation by increasing chemokine production. IL-17F also stimulates induction of other pro-inflammatory cytokines TNF alpha, IL-1 beta, IL-6, and IL-8, and reports strongly suggest the involvement of IL-17 in several chronic inflammatory diseases such as rheumatoid arthritis, psoriasis and multiple sclerosis. TGF-beta (differentiation) and IL-23 (expansion) are required for induction and maintece of Th17 (IL-17 producing) cells, which in turn induce the other pro-inflammatory cytokines. IL-17F is produced, and exists, as a homo-dimer, with homology to a herpes virus early protein, is one of the six members (IL-17A-F) of this cytokine family, and is well characterized and highly expressed by activated effector memory T cells. IL-17F has been found to inhibit the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1.
|Functional Assay, Neutralization|
|PBS with no preservative; pH 7.2|
For Research Use Only.
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