Interleukin-35 inhibits angiogenesis through T helper17/ Interleukin-17 related signaling pathways in IL-1?-stimulated SW1353 cells

Background: Angiogenesis associates with chondrocytes differentiation in inflammatory arthritis. Interleukin (IL)- 1 beta stimulated SW1353 cells have a phenotype similar to this kind of chondrocytes. IL-17A, a target in T helper 17 (Th17)/IL-17 signaling pathways, was expressed by SW1353 cells. The study aimed to explore the role of IL-35 on angiogenesis in IL-1 beta stimulated SW1353 cells and its related signaling pathways. Methods: Microarray dataset was downloaded from the Gene Expression Omnibus database of arthritis cartilage. The protein-protein interaction (PPI) was analyzed for IL-35, pro-angiogenic factors and the differentially expressed genes (DEGs). We studied the effects of IL-35 on proliferation and apoptosis in IL-1 beta stimulated SW1353 cells using cell counting kit-8 (CCK-8) assay and flow cytometry. The expression of pro-angiogenic factors and IL-17A were assessed by western blot and real-time PCR. Added plumbagin (inhibitor of IL-17A) to repeat the above experiment. The secretion of IL-17A was assessed by ELISA. Results: IL-35, pro-angiogenic factors interacted with DEGs to affect the function of arthritis chondrocytes. IL-35 promoted IL-1 beta-stimulated SW1353 cells proliferation, inhibited apoptosis, and decreased pro-angiogenic molecules and IL-17A expression in a concentration dependent manner. IL-35 inhibited IL-17A secretion in the supernatants of these cells. Blocking the Th17/IL-17 related pathways with plumbagin abolished the effects of IL-35 on IL-1 beta-stimulated SW1353 cells. Conclusion: These results suggested that IL-35 regulated differentiation and pro-angiogenic molecules expression in IL-1 beta stimulated SW1353 cells via Th17/IL-17 related signaling pathways. Our findings may reveal the mechanisms of novel angiogenesis molecules in inflammatory chondrocyte lesion.