Stromal cell‐derived factor(SDF)‐1 induces RANKL in Rheumatoid Arthritis synovial fibroblasts and CD4+ T cells

Abstract

BACKGROUDSDF‐1 is a chemokine promoting the migration of inflammatory cells into the inflamed synovium in rheumatoid arthritis.OBJECTIVEThis study aims to determine the effect and mechanism of SDF‐1 on bony destructive process in RA through RANKL regulation from synovial fibroblasts and CD4+ T cells.METHODSynovial fibroblasts were isolated from synovial tissues of RA patients and CD4+ T cells were isolated from PBMC of RA patients. After RA synovial fibroblasts and CD4+ T cells were treated with rhSDF‐1, the expression of RANKL mRNA was determined using real‐time PCR.RESULTSThe expression of RANKL mRNA in RA synovial fibroblasts and CD4+ T cells was increased after SDF‐1 stimulation in a dose dependent manner. After RA synovial fibroblasts were culture with neutralizing antibodies of TNF‐α and IL‐6, the expression of RANKL mRNA was decreased in RA synovial fibroblasts. SDF‐1‐induced RANKL expression was also diminished after inhibition of PI3 kinase, p38 MAP kinase, and JNK.CONCLUSIONThis result suggests that SDF‐1 could induce RANKL from RA synovial fibroblasts mediated by TNF‐α and IL‐ 6. In RA CD4+ T cells, SDF‐1‐induced RANKL expression is mediated by IL‐1β as well as TNF‐α and IL‐6.This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF‐2010‐ NRF‐ 2010‐R1A4A002‐0008205)