The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium.
OBJECTIVE
Reactive oxygen intermediates play an important role in the inflammatory processes of rheumatoid arthritis. Cyclooxygenase-2 is an inducible form of an enzyme involved in prostanoid biosynthesis. This study linked peroxynitrite (ONOO-) to the signaling pathways that induce COX-2.


RESULTS
Exposure of rheumatoid synovial cells to peroxynitrite resulted in COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in peroxynitrite-treated rheumatoid synovial cells. Dexamethasone markedly inhibited this peroxynitrite-mediated COX-2 expression at therapeutic concentrations.


CONCLUSIONS
This study demonstrates that oxidant stress is an important inducer of COX-2 in rheumatoid synovium. This induction may contribute to the amplification of prostanoids in the rheumatoid inflammatory process.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan. migita@net.nagasaki-u.ac.jp
Yamasaki
S
S
Ida
H
H
Kita
M
M
Hida
A
A
Shibatomi
K
K
Kawakami
A
A
Aoyagi
T
T
Eguchi
K
K
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology*
D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D011451:Prostaglandin-Endoperoxide Synthases