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

Objective, Taurine chloramine (Tau-Cl) has been shown to inhibit the produc tion of proinflammatory cytokines (interleukin-6 [IL-6] and IL-8) by fibrob lastlike synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patient s, 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 kappa B (NF-kappa B) a nd activator protein 1 (AP-1) transcription factors, which are crucial for the transcription of these cytokine genes, were investigated in FLS isolate d from the synovial tissue of RA patients. FLS were cultured in vitro for 3 -6 passages and stimulated with recombinant human IL-1 beta (1 ng/ mi) in t he presence of either Tau or Tau-Cl, which were added simultaneously with t he stimulus at concentrations of 250 mu M or 500 mu M. The relative express ion of IL-6 and IL-8 messenger RNA (mRNA) was evaluated after 4 hours of st imulation, using competitive reverse transcriptase-polymerase chain reactio n. The DNA binding activity of NF-kappa B and AP-1 was examined 30 minutes and 2 hours after cell stimulation, respectively, using electromobility gel shift assay. Results. IL-1 beta triggered a significant rise in the activity of transcri ption factors NF-kappa B and AP-1, followed by an elevation of cytokine IL- 6 and IL-8 mRNA expression. Tau-Cl, but not Tau, reduced IL-1 beta-triggere d cytokine mRNA expression, exerting stronger inhibitory activity on the le vels of IL-6 than on those of IL-8, Importantly, Tau-Cl also diminished the activity of NF-kappa B and, to a lesser extent, that of AP-1 transcription factor. Neither IL-1 beta nor Tau-Cl affected the activity of octamer tran scription factor 1, Conclusion. Tau-Cl inhibition of IL-6 and IL-8 synthesis in FLS from RA pat ients results from the ability of this compound to diminish the activity of the major transcriptional regulators (NF-kappa B and AP-1), which subseque ntly reduces the transcription of these cytokine genes.