Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells.
Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.
Honda
S
S
First Department of Internal Medicine, Kurume University School of Medicine.
Migita
K
K
Hirai
Y
Y
Ueki
Y
Y
Yamasaki
S
S
Urayama
S
S
Kawabe
Y
Y
Fukuda
T
T
Kawakami
A
A
Kamachi
M
M
Kita
M
M
Ida
H
H
Aoyagi
T
T
Eguchi
K
K
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*
D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010396:Penicillamine