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Scientific article
Open access
English

Expression and function of junctional adhesion molecule-C in human and experimental arthritis

Published inArthritis research & therapy, vol. 9, no. 4, R65
Publication date2007
Abstract

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 +/- 1.3 arbitrary units in RA versus 3.3 +/- 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 +/- 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 +/- 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis.

Keywords
  • Adoptive Transfer
  • Animals
  • Antibodies, Blocking/pharmacology
  • Arthritis, Experimental/drug therapy/ metabolism/pathology
  • Arthritis, Rheumatoid/ metabolism/pathology
  • Cell Adhesion Molecules/genetics/immunology/ metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Fibroblasts/drug effects/metabolism/pathology
  • Gene Expression
  • Humans
  • Immunoglobulins/genetics/immunology/ metabolism
  • Macrophages
  • Male
  • Membrane Proteins/genetics/immunology/ metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neutrophils
  • Osteoarthritis/ metabolism/pathology
  • RNA, Messenger/metabolism
  • Serum Amyloid A Protein/analysis
  • Spleen/drug effects/pathology
  • Synovial Membrane/chemistry/ metabolism
  • T-Lymphocytes/drug effects/pathology
Citation (ISO format)
PALMER-LOURENCO, Gaby et al. Expression and function of junctional adhesion molecule-C in human and experimental arthritis. In: Arthritis research & therapy, 2007, vol. 9, n° 4, p. R65. doi: 10.1186/ar2223
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ISSN of the journal1478-6354
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