Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes

Objective. To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-Cl), affects proliferation of, and proi nflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibrobl ast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patient s. Methods. FLS, isolated from the synovial tissue of 19 RA patients and cultu red in vitro for 3-6 passages, were stimulated with the recombinant human c ytokines IL-1 beta (1 ng/ml), tumor necrosis factor alpha (TNF alpha; 10 ng /ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which we re added at concentrations of 50-500 mu M. Tau and Tau-Cl were added simult aneously with, 2 hours before, or 24 hours after the stimuli. The concentra tions of IL-6 and IL-8 were determined in culture supernatants using specif ic enzyme-linked immunosorbent assays. Proliferation of FLS was estimated o n the basis of H-3-thymidine incorporation into the cells, which were cultu red for 72 hours in the presence of recombinant human basic fibroblast grow th factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneous ly at the beginning of the culture. Results. Cultured in vitro, RA FLS spontaneously secreted low levels of IL- 6 and IL-8, but when RA FLS were stimulated with IL-1 beta, TNF alpha, or I L-17, significantly higher amounts of IL-6 and IL-8 were produced. Tau-Cl, but not Tau, inhibited cytokine-triggered synthesis of IL-6 (50% inhibitory concentration [IC50] similar to 225 mu M) and IL-8 (IC50 similar to 450 mu M) when added simultaneously wit the stimuli. However, IL-17-induced produ ction of IL-8 was not affected by Tau-Cl. In the cells prestimulated with I L-1 beta for 24 hours, Tau-Cl still inhibited synthesis of IL-6, but did no t affect IL-8 production. Moreover, Tau-Cl inhibited spontaneous and bFGF-t riggered proliferation of FLS in a a dose-dependent manner. Neither Tau or Tau-Cl affected cel viability. Conclusion. The results of these studies demonstrate that Tau-Cl inhibits p roduction of proinflammatory cytokines by RA FLS, as well as proliferation of these cells. Thus, Tau-Cl may act as a physiologic modulator of FLS func tions related to their pathogenic role in RA.