Induction of COX-2 Expression by Nitric Oxide in Rheumatoid Synovial Cells

• Published in: Biochemical and biophysical research communications Vol. 268; no. 3; pp. 928 - 931
• Main Authors: Honda, Seiyo, Migita, Kiyoshi, Hirai, Yasuko, Ueki, Yukitaka, Yamasaki, Satoshi, Urayama, Satoshi, Kawabe, Yojiro, Fukuda, Takaaki, Kawakami, Atsushi, Kamachi, Makoto, Kita, Masako, Ida, Hiroaki, Aoyagi, Takahiko, Eguchi, Katsumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.02.2000
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Base Sequence; Cells, Cultured; COX-2 protein; Cyclooxygenase 2; dexamethasone; DNA Primers - genetics; Enzyme Induction - drug effects; Gene Expression - drug effects; Humans; Isoenzymes - biosynthesis; Isoenzymes - genetics; Membrane Proteins; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Osteoarthritis - genetics; Osteoarthritis - metabolism; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Synovial Membrane - drug effects; Synovial Membrane - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.2228

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.