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


CONCLUSIONS
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.
Kontny
Ewa
E
Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland.
Rudnicka
Weronika
W
Kowalczewski
Jacek
J
Marcinkiewicz
Janusz
J
Maslinski
Wlodzimierz
W
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013654:Taurine; C043410:N-chlorotaurine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone