Nitric oxide synthase and cyclooxygenases: distribution, regulation, and intervention in arthritis.
Nitric oxide (NO) and prostaglandin E2 (PGE2) are two pleiotropic inflammatory mediators overproduced in arthritis-affected joints. The inducible isoform of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) are found both in the synovial tissue and in the cartilage. Their expression is regulated by catabolic cytokines, such as interleukin-1beta and tumor necrosis factor-alpha. These inflammatory mediators play a profound role in the pathogenic processes that arise in the pannus of rheumatoid arthritis and also interfere with cartilage homeostasis in osteoarthritis. Several drugs, including nonsteroidal anti-inflammatory drugs, immunosuppressive agents, and tetracyclines, attenuate the activity of NO and PGE2. These pleiotropic mediators are targets for pharmacologic intervention and gene therapy.
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*