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Stromal cell‐derived factor(SDF)‐1 induces RANKL in Rheumatoid Arthritis synovial fibroblasts and CD4+ T cells
Author(s) -
Kim Kyoung-Woon,
Kim Hae-Rim,
Kim Bo-Mi,
Cho Mi-La,
Lee Sang-Heon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.655.5
Subject(s) - rankl , stromal cell , tumor necrosis factor alpha , chemokine , cancer research , chemistry , medicine , immunology , inflammation , microbiology and biotechnology , activator (genetics) , biology , receptor
BACKGROUD SDF‐1 is a chemokine promoting the migration of inflammatory cells into the inflamed synovium in rheumatoid arthritis. OBJECTIVE This 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. METHOD Synovial 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. RESULTS The 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. CONCLUSION This 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)