Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts

Arthritis Rheum. 1990 Dec;33(12):1776-86. doi: 10.1002/art.1780331204.

Abstract

This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN gamma) each increased the cell surface expression of intercellular adhesion molecule 1 (ICAM-1) on human synovial fibroblasts in a dose- and time-dependent manner. Maximal ICAM-1 expression occurred within 8 hours of induction, with the following order of efficacy: IFN gamma greater than TNF alpha greater than IL-1 beta. The number of cells bearing the ICAM-1 antigen also increased, from a basal level of approximately 30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM-1 expression rapidly decreased following cytokine removal. The expression of lymphocyte function-associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFN gamma induced HLA class II antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL-6 and granulocyte-macrophage colony-stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis.

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • CD58 Antigens
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flow Cytometry
  • Gene Expression / drug effects
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Radioimmunoassay
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Synovitis / etiology*
  • Synovitis / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Antigens, Surface
  • CD58 Antigens
  • Cell Adhesion Molecules
  • Cytokines
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Interleukin-1
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma