Selective inhibition of cyclooxygenase 2–generated prostaglandin E₂ synthesis in rheumatoid arthritis synoviocytes by taurine chloramine

Abstract

Objective. To investigate the effects of taurine chloramine (Tau-Cl), a chlorinated derivative of the amino acid taurine, on the expression of cyclooxygenase (COX) isoenzymes and prostaglandin E 2 (PGE 2 ) synthesis in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS).Methods. FLS, isolated from the synovial tissue of RA patients, were treated in vitro with either interleukin-1␤ (IL-1␤; 1 ng/ml) alone or together with 200-500 M Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase chain reaction) levels. The concentration of PGE 2 was measured by competitive acetylcholinesterase enzyme immunoassay.Results. Resting FLS expressed mRNA encoding both COX-1 and COX-2, but only COX-1 was present at the protein level. These cells produced negligible amounts of PGE 2 . Upon stimulation with IL-1␤, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE 2 synthesis. In the presence of 300-400 M Tau-Cl, significant inhibition of IL-1␤-triggered COX-2 mRNA and protein, and a related decrease in PGE 2 production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted.Conclusion. Tau-Cl inhibits IL-1␤-triggered elevation of COX-2 and generation of PGE 2 by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

Inhibitory effects of the Gentiana macrophylla (Gentianaceae) extract on rheumatoid arthritis of rats

“…When rats were administered the Gentiana macrophylla extract, the PGE 2 level was apparently decreased (Table 1) and the damage to auriculare erythema and tail tubercle was significantly reduced. Since increasing PGE 2 can cause inflammatory reactions, such as local congestion, edema, and pain in rheumatoid arthritis (Kontny et al, 2003;Fogel-Petrovic et al, 2004), the significant decrease of PGE 2 in rheumatoid rats may be due to inhibition of COX2 activity following the administration of Gentiana macrophylla.…”

Taurine chloramine inhibits proliferation of rheumatoid arthritis synoviocytes by triggering a p53-dependent pathway

“…Finally, we propose that due to anti-infl ammatory [25][26][27][28] and anti-proliferative (present results) effects triggered in RA FLS, Tau-Cl may represent the new therapeutic strategy to normalize abnormal behaviour of these cells. Our data showing protection of subcutaneously applied Tau-Cl against development of collagen-induced arthritis in mice [57], provide support for this notion.…”

“…The sequence of primers specifi c for p21 and PCR conditions were as described previously [38] with the modifi cation that the primers annealing temperature was performed at 50 °C. The primers specifi c for survivin and for the housekeeping gene encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as well as PCR conditions, were as described previously [27,39]. Under applied conditions, the rate of particular product amplifi cation was within the exponential rate.…”

“…It is possible that the blockade of RA FLS cell-cycle progression may represent novel therapeutic approach for RA treatment. We have previously found that taurine chloramine (Tau-Cl), a physiologic compound of known anti-infl ammatory activities, inhibits not only some pro-infl ammatory functions of RA FLS [25][26][27][28][29] but also proliferation of these cells [25,29]. Taurine chloramine is generated by activated neutrophils in a reaction of hypochlorous acid (HOCl) with b-amino acid taurine (Tau) [30].…”

Anti-inflammatory activity ofGentiana striataMaxim.

“…When rats were administered the EGS, the PGE 2 level decreased (Table 1) and the damage to auriculare erythema and tail tubercle was significantly reduced. Since increasing PGE 2 can cause inflammatory reactions, such as local congestion, oedema and pain in RA (Fogel-Petrovic, Long, Knight, Thompson, & Upham, 2004;Kontny, Rudnicka, Kowalczewski, Marcinkiewicz, & Maslinski, 2003), the significant decrease of PGE 2 in rheumatoid rats may be due to inhibition of COX 2 activity following the administration of EGS.…”