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

Arthritis Rheum. 2003 Jun;48(6):1551-5. doi: 10.1002/art.10975.

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-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500 microM 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-1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl, significant inhibition of IL-1beta-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-1beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Blotting, Western
  • Cells, Cultured
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis*
  • Dinoprostone / genetics
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Interleukin-1 / pharmacology
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Male
  • Membrane Proteins
  • Middle Aged
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Messenger / metabolism
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Taurine / analogs & derivatives*
  • Taurine / pharmacology*

Substances

  • Drug Combinations
  • Enzyme Inhibitors
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Taurine
  • N-chlorotaurine
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone