The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid arthritis fibroblast-like synoviocytes

Arthritis Rheum. 2000 Oct;43(10):2169-77. doi: 10.1002/1529-0131(200010)43:10<2169::AID-ANR4>3.0.CO;2-#.


Objective: Taurine chloramine (Tau-Cl) has been shown to inhibit the production of proinflammatory cytokines (interleukin-6 [IL-6] and IL-8) by fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. The present study was conducted to elucidate the mechanism of inhibitory action exerted by Tau-Cl.

Methods: The effects of Tau-Cl on 1) the transcription of genes coding for IL-6 and IL-8, and 2) the activity of nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors, which are crucial for the transcription of these cytokine genes, were investigated in FLS isolated from the synovial tissue of RA patients. FLS were cultured in vitro for 3-6 passages and stimulated with recombinant human IL-1beta (1 ng/ml) in the presence of either Tau or Tau-Cl, which were added simultaneously with the stimulus at concentrations of 250 microM or 500 microM. The relative expression of IL-6 and IL-8 messenger RNA (mRNA) was evaluated after 4 hours of stimulation, using competitive reverse transcriptase-polymerase chain reaction. The DNA binding activity of NF-kappaB and AP-1 was examined 30 minutes and 2 hours after cell stimulation, respectively, using electromobility gel shift assay.

Results: IL-1beta triggered a significant rise in the activity of transcription factors NF-kappaB and AP-1, followed by an elevation of cytokine IL-6 and IL-8 mRNA expression. Tau-Cl, but not Tau, reduced IL-1beta-triggered cytokine mRNA expression, exerting stronger inhibitory activity on the levels of IL-6 than on those of IL-8. Importantly, Tau-Cl also diminished the activity of NF-kappaB and, to a lesser extent, that of AP-1 transcription factor. Neither IL-1beta nor Tau-Cl affected the activity of octamer transcription factor 1.

Conclusion: Tau-Cl inhibition of IL-6 and IL-8 synthesis in FLS from RA patients results from the ability of this compound to diminish the activity of the major transcriptional regulators (NF-kappaB and AP-1), which subsequently reduces the transcription of these cytokine genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • DNA-Binding Proteins / drug effects
  • Female
  • Fibroblasts / cytology*
  • Host Cell Factor C1
  • Humans
  • Inflammation Mediators / pharmacology*
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Male
  • Middle Aged
  • NF-kappa B / drug effects
  • Octamer Transcription Factor-1
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Taurine / analogs & derivatives*
  • Taurine / pharmacology*
  • Transcription Factor AP-1 / drug effects
  • Transcription Factors / drug effects
  • Transcription, Genetic / drug effects


  • DNA-Binding Proteins
  • HCFC1 protein, human
  • Host Cell Factor C1
  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Transcription Factor AP-1
  • Transcription Factors
  • Taurine
  • N-chlorotaurine