J Korean Rheum Assoc.  2005 Jun;12(2):73-82.

Regulation of betaig-h3 Production in Rheumatoid Synovitis by Inflammatory Mediators

Affiliations
  • 1Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. ymkang@knu.ac.kr
  • 2Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
  • 3Departments of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu, Korea.
  • 4Departments of Immunology, Kyungpook National University School of Medicine, Daegu, Korea.
  • 5Departments of Biochemistry, Kyungpook National University School of Medicine, Daegu, Korea.

Abstract


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.

Keyword

Rheumatoid arthritis; Transforming growth factor-beta-inducible gene-h3; Fibroblast-like synoviocyte

MeSH Terms

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
Cytokines
Dexamethasone
Interleukin-10
Interleukin-4
Interleukin-6
Transforming Growth Factor beta
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha
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