Up-regulated transforming growth factor β-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through αvβ3 integrin: Regulation by cytokines

Eon Jeong Nam, Keum Hee Sa, Dong Wan You, Jang Hee Cho, Jae Seok Seo, Seung Woo Han, Jae Yong Park, Sung Il Kim, Hee Soo Kyung, In San Kim, Young Mo Kang

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39 Citations (Scopus)

Abstract

Objective. To delineate the expression of transforming growth factor β-inducible gene h3 (βIG-H3) in rheumatoid synovitis and to determine the regulatory role of βIG-H3 in the adhesion and migration of fibroblast-Iike synoviocytes (FLS). Methods. Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of βIG-H3 within rheumatoid synovium. Synthesis of βIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of βIG-H3 and function-blocking antibodies to integrins. Results. Expression of βIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced βIG-H3, which was up-regniated by transforming growth factor β1, interleukin-1β, and tumor necrosis factor α. Although FLS expressed a variety of integrins, βIG-H3 mediated adhesion and migration of FLS through interaction with αvβ3 integrin. Cytokines failed to affect the βIG-H3-mediated adhesion. However, migration of FLS guided by βIG-H3 was enhanced by interferon-γ and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of βIG-H3 inhibited adhesion and migration in a dose-dependent manner. Conclusion. The results suggest that βIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of βIG-H3 and αvβ3 integrin-interacting motifs as potential therapeutic targets in this disease.

Original languageEnglish
Pages (from-to)2734-2744
Number of pages11
JournalArthritis and Rheumatism
Volume54
Issue number9
DOIs
Publication statusPublished - 2006 Sep 1
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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