IL-6 Secretion Induced by IL‑17F and Neutralization by Human IL‑17F Antibody. Recombinant Human IL‑17F induces IL-6 secretion in the NIH‑3T3 mouse embryonic fibroblast cell line in a dose-dependent response (orange line), as measured by the Mouse IL-6 Quantikine kit (Catalog # M6000B). Under these conditions, IL-6 secretion elicited by IL‑17F is neutralized (green line) by increasing concentrations of Mouse Anti-Human IL‑17F Monoclonal Antibody (Catalog # MAB13352). The ND50 is typically 0.1-0.6 μg/mL.|
The Interleukin 17 (IL-17) family proteins, comprising six members (IL-17A through IL-17F), are secreted, structurally related proteins that share a conserved cystine‑knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus. With the exception of IL-17B, which exists as a non-covalently linked dimer, all IL-17 family members are disulfide-linked dimers. IL-17 family proteins are pro-inflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions (1, 2).
Human IL-17F cDNA encodes a 163 aa protein with a putative 30 aa signal peptide. Among IL-17 family members, IL-17F is most closely related to IL-17A (approximately 44% aa sequence homology), but shares only limited sequence homology (16 - 30%) with IL-17B, C, D and E. Human and mouse IL-17F share 55% sequence identity. IL-17F is expressed in activated CD4+ T-cells and activated monocytes. Five receptors (IL-17 RA, B, C, D and E) have been identified (5). Although the ligands for IL-17 RD and E are not known yet, it is reported that IL-17 RA binds IL-17A, and IL-17 RB binds IL-17B and IL-17E. IL-17 RC binds IL-17A and IL-17F with similarly high affinity and functions as a receptor for both IL-17A and IL-17F (5, 6). The biological activities mediated by IL-17F are similar to those of IL‑17. IL‑17F stimulates production of IL-6, IL-8, G-CSF, and regulates cartilage matrix turnover by increasing matrix release and inhibiting new matrix synthesis (4). IL‑17F also inhibits angiogenesis and induces production of IL-2, TGF-beta, and monocyte chemoattractant protein-1 in endothelial cells (3).
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