Nitric oxide enhances cyclooxygenase activity in articular cartilage.
Nitric oxide (NO) is a small messenger molecule synthesized by a family of enzymes, the nitric oxide synthases. Cyclooxygenases are a group of proinflammatory enzymes that release prostaglandins including prostaglandin E2 (PGE2). Both nitric oxide synthase and cyclooxygenase are involved in the inflammatory cascade of arthritis. However, the relationship between these two enzymes and their products has not been explored in articular cartilage. Here we show that in cultured bovine chondrocytes and explants of human osteoarthritic cartilage both nitric oxide synthase and cyclooxygenase activities were induced by the inflammatory mediators, lipopolysaccharide, and interleukin-1 beta or tumor necrosis factor-alpha. When nitric oxide synthase activity was inhibited, PGE2, synthesis was inhibited. NO donors also induced PGE2 synthesis and NO scavengers inhibited cyclooxygenase activity. Taken together, these results support the concept that PGE2 synthesis is directly related to NO formation and that NO may modulate cyclooxygenase activity in articular cartilage.
Manfield
L
L
Hospital for Special Surgery, Cornell University Medical College, New York, NY, USA.
Jang
D
D
Murrell
G A
GA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology*; D002417:Cattle; D002478:Cells, Cultured; D002648:Child; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013467:Sulindac / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013467:Sulindac; D009569:Nitric Oxide; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone