title: Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through alpha v beta3 integrin: Regulation by cytokines.
abstract: OBJECTIVE
  To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like 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 betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-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 betaIG-H3 and function-blocking antibodies to integrins.
  
  
  RESULTS
  Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner.
  
  
  CONCLUSIONS
  The results suggest that betaIG-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 betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.
authors.affiliation: Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Eon Jeong
authors.initials: EJ
authors.lastname: Nam
authors.forename: Keum Hee
authors.initials: KH
authors.lastname: Sa
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: You
authors.forename: Jang Hee
authors.initials: JH
authors.lastname: Cho
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Seo
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Han
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Hee Soo
authors.initials: HS
authors.lastname: Kyung
authors.forename: In San
authors.initials: IS
authors.lastname: Kim
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000601:surgery; D019643:Arthroplasty, Replacement; D002448:Cell Adhesion; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics*; D007700:Kinetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D000099222:betaIG-H3 Protein
chemical_list: D016207:Cytokines; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D012313:RNA; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein