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

Authors


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 E2 (PGE2) 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-1β (IL-1β; 1 ng/ml) alone or together with 200–500 μM 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 PGE2 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 PGE2. Upon stimulation with IL-1β, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE2 synthesis. In the presence of 300–400 μM Tau-Cl, significant inhibition of IL-1β–triggered COX-2 mRNA and protein, and a related decrease in PGE2 production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted.

Conclusion

Tau-Cl inhibits IL-1β–triggered elevation of COX-2 and generation of PGE2 by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

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