IL-6 Secretion Induced by IL‑17 and Neutralization by Canine IL‑17 Antibody. |
Recombinant Canine IL‑17 (Catalog # 5848-CL) induces IL-6 secretion in the NIH‑3T3 mouse embryonic fibroblast cell line in a dose-dependent manner (orange line). IL-6 Secretion elicited by Recombinant Canine IL‑17 (5 ng/mL) is neutralized (green line) by increasing concentrations of Mouse Anti-Canine IL‑17 Monoclonal Antibody (Catalog # MAB5848). The ND50 is typically 5-30 ng/mL.
Interleukin 17 (IL-17; also IL-17A and CTLA-8) is a 17 kDa member of the IL-17 family of cytokines (1). Members of this family demonstrate a structural motif termed a cysteine knot which characterize a large superfamily of growth factors. Although most cysteine knot superfamily members use three intrachain disulfide bonds to create a knot, IL-17 family molecules generate the same structural form with only two disulfide links (2-4). Based on the amino acid (aa) sequence alignment with human IL-17, canine IL-17 is 130 aa in length. It is secreted as a 35 kDa disulfide-linked homodimer and as a 40 kDa disulfide-linked heterodimer with IL-17F (5). Canine IL‑17 is 81% identical on the aa level to human IL-17. IL-23 drives Th17 lymphocytes to produce IL-17 (6-8). IL-17’s production has also been demonstrated in gamma δ T cells (9), CD8+ memory T cells (10-11), eosinophils (12), neutrophils (10), and monocytes (13). Studies have identified that the widely expressed receptors IL‑17RA and IL-17RC form a heterodimer for the binding of IL-17 (6, 14-15). The predominant function of IL-17 is thought to be as a proinflammatory mediator through a variety of mechanisms (16). Locally, IL‑17 stimulates production of IL-6, prostaglandin E and nitric oxide (16-19), and synergy with other inflammatory cytokines such as TNF-alpha, IL‑1 beta and IFN -gamma leads to up-regulation of gene expression and progression and amplification of local inflammation (16, 20-22). IL‑17 also mediates chemotaxis of neutrophils and monocytes to sites of inflammation through the chemoattractant mediators IL-8, GRO‑ alpha, and MCP-1 (16, 22-25) while augmenting production of hematopoietic growth factors, such as G-CSF and GM-CSF (16, 26, 27), which promote the growth and maturation of the recruited myeloid cells. In addition, IL-17 serves as a bridge between innate and adaptive immune responses by enhancing the induction of co-stimulatory molecules such as ICAM-1 and other cytokines (16, 22, 28), thereby supporting T cell activation. IL-17 expression has been associated with many inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, asthma, systemic lupus erythematosus and allograft rejection (15).
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