Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts

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Objective: Angiogenesis is a process stimulated in inflamed synovium of patients with osteoarthritis (OA), and contributes to the progression of the disease. Synovial fibroblasts secrete angiogenic factors, such as vascular endothelial growth factor (VEGF), an up-regulator of angiogenesis, and this ability is increased by interleukin (IL)-1β. The purpose of this study was to verify whether IL-17 contributes and/or synergizes with IL-1β and tumor necrosis factor (TNF)-α in vessel development in articular tissues by stimulating the secretion of proangiogenic factors by synovial fibroblasts. Design: We stimulated in vitro synovial fibroblasts isolated from OA, rheumatoid arthritis (RA) and fractured patients (FP) with IL-17 and IL-1β and from OA patients with IL-17, IL-1β and TNF-α. In the supernatants from the cultures, we assayed the amount of VEGF by immunoassay and other angiogenic factors (keratinocyte growth factor, KGF; hepatocyte growth factor, HGF; heparin-binding endothelial growth factor, HB-EGF; angiopoietin-2, Ang-2; platelet-derived growth factor B, PDGF-BB; thrombopoietin, TPO) by chemiluminescence; semiquantitative RT-PCR was used to state mRNA expression of nonreleased angiogenic factors (Ang-2 and PDGF-BB) and tissue inhibitors of metalloproteinase (TIMP)-1. Results: IL-17, TNF-α and IL-1β increased VEGF secretion by synovial fibroblasts from OA patients. IL-17 and IL-1β also increased VEGF secretion in RA and FP. Besides, IL-17 increased KGF and HGF secretions in OA, RA and FP; in OA and RA, IL-17 also increased the HB-EGF secretion and the expression of TIMP-1 as protein and mRNA. In OA patients IL-17 had an additive effect on TNF-α-stimulated VEGF secretion. Conclusions: These results suggest that IL-17 is an in vitro stimulator of angiogenic factor release, both by its own action and by cooperating with TNF-α. © 2005 OsteoArthritis Research Society International.




Honorati, M. C., Neri, S., Cattini, L., & Facchini, A. (2006). Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthritis and Cartilage, 14(4), 345–352.

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