Glucocorticoid-mediated repression of inflammatory cytokine production in fibroblast-like rheumatoid synoviocytes is independent of nuclear factor-kappaB activation induced by tumour necrosis factor alpha

Rheumatology (Oxford). 2001 Mar;40(3):267-73. doi: 10.1093/rheumatology/40.3.267.


Objective: To determine whether steroids inhibit the production of inflammatory cytokines by the inhibition of nuclear factor kappaB (NF-kappaB) activation in fibroblast-like rheumatoid synoviocytes (FLSs) under inflammatory conditions, and to determine whether steroids stimulate the induction of synthesis of the inhibitory protein IkappaB-alpha in the anti-inflammatory immune response of these cells.

Methods: Expression of the interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) genes was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the secreted IL-6 was measured with the enzyme-linked immunosorbent assay. Inhibition of the NF-kappaB activation was examined with the electrophoretic mobility shift assay (EMSA). In order to study dexamethasone (DEX)-dependent regulation of IkappaB-alpha expression, we performed Western blotting before and after stimulation with tumour necrosis factor alpha (TNF-alpha).

Results: The inflammatory cytokine study showed that DEX suppressed gene expression and the production of protein in FLSs. EMSA demonstrated that identical amounts of NF-kappaB were present in the nucleus of the FLSs stimulated by TNF-alpha, with or without pretreatment with DEX. Treatment of FLSs with DEX did not induce an increase in IkappaB-alpha sufficient to prevent nuclear translocation of NF-kappaB on stimulation with TNF-alpha.

Conclusion: DEX may suppress the production of inflammatory cytokines, such as IL-6 and IL-1beta, but it neither prevents the translocation of NF-kappaB to the nucleus nor induces the synthesis of IkappaB-alpha protein in FLSs stimulated by TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / physiopathology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Cytokines / biosynthesis*
  • Cytokines / drug effects
  • DNA-Binding Proteins / metabolism
  • Dexamethasone / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation / physiology
  • Glucocorticoids / pharmacology*
  • Humans
  • I-kappa B Proteins*
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Cytokines
  • DNA-Binding Proteins
  • Glucocorticoids
  • I-kappa B Proteins
  • Interleukin-1
  • Interleukin-6
  • NF-kappa B
  • NFKBIA protein, human
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Dexamethasone