Expression of the interleukin 6 gene in rheumatoid synovial fibroblasts

J Rheumatol. 1990 Dec;17(12):1608-12.

Abstract

A number of fibroblastoid synovial cell lines have been established from rheumatoid joints. These cell lines were shown to express the interleukin 6 (IL-6) gene constitutively, and exposure of these cells to 5 ng/ml of recombinant human interleukin 1 beta (IL-1 beta) increased IL-6 gene expression. Other recombinant human lymphokines, namely interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor had no enhancing effect on IL-6 gene expression. Dexamethasone added to the cultures at 10(-7) M concentration suppressed the constitutive expression of the IL-6 gene. At a concentration of 10(-5) M, dexamethasone partially suppressed the IL-1 enhanced expression of IL-6. The IL-6 gene probe also hybridized to RNA from unfractionated synovial fluid cells, peripheral blood T cells and non-T cells but not Epstein-Barr virus transformed peripheral blood B cells of patients with rheumatoid arthritis. Our results suggest that in rheumatoid arthritis, synovial fibroblasts actively participate in joint inflammation by lymphokine production. The coexpression of both IL-1 and IL-6 by one synovial fibroblast line suggests a mechanism for the perpetuation of synovitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Dexamethasone / pharmacology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Lymphokines / pharmacology
  • RNA / drug effects
  • RNA / genetics
  • RNA / metabolism
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Synovitis / metabolism
  • Synovitis / pathology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Histocompatibility Antigens Class II
  • Interleukin-1
  • Interleukin-6
  • Lymphokines
  • Tumor Necrosis Factor-alpha
  • RNA
  • Dexamethasone
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor