OBJECTIVE: To investigate the expression pattern of transforming growth factor-beta-inducible gene-h3 (betaig-h3) within rheumatoid synovial tissue and the regulation of betaig-h3 synthesis in fibroblast-like synoviocyte (FLS). METHODS: Synovial tissues obtained from patients with rheumatoid arthritis and osteoarthritis were obtained during joint replacement surgery. betaig-h3 expression was evaluated with immunohistochemical stain. FLS was isolated from synovial tissues and stimulated with cytokines including TGF-beta, TNF-alpha, IL-1beta, IFN-gamma, IL-6, IL-4, and IL-10. betaig-h3 synthesis was measured using semiquantitative RT-PCR, ELISA, immunofluorescence stain, and flow cytometry. RESULTS: Expression of betaig-h3 was diffuse and abundant in both lining and sublining layers of rheumatoid synovium, which was more prominent than those of osteoarthritis. Production of betaig-h3 in FLS was regulated by TGF-beta1 in a dose-dependent manner and was highest at 5 ng/mL of TGF-beta1. TNF-alpha and IL-1beta upregulated the production of betaig-h3 from FLS synergistically with TGF-beta1 but other cytokines such as IL-4, IL-6, IL-10 did not affect. betaig-h3 synthesis was efficiently inhibited by dexamethasone at higher dose (100 nM) but not by cyclosporine-A. CONCLUSION: Production of betaig-h3, which is highly upregulated in rheumatoid synovitis, is differentially regulated by inflammatory cytokines.
Arthritis, Rheumatoid ; Cytokines ; Dexamethasone ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Joints ; Osteoarthritis ; Synovial Membrane ; Synovitis* ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Tumor Necrosis Factor-alpha