Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation.
Nitric oxide (NO) and prostaglandin (PG) E2 produced by NO synthase type 2 (NOS2) and cyclooxygenase type 2 (COX2), respectively, are important mediators in inflammation. There is much information regarding their roles in models of inflammation in mice and in humans with diseases such as rheumatoid arthritis (RA). A variety of stimuli including cytokines, microbial components, immune complexes, and mechanical stress can induce both NOS2 and COX2 mRNA transcription and protein synthesis and enhance inflammation. This has been demonstrated in both mice and humans. NOS2-specific inhibitors reduce inflammation in mice, and COX2-specific inhibitors reduce inflammation in mice and in humans. There is significant cross-talk between PGE2/NO and COX2/NOS2. Treatments that inhibit both NOS2 and COX2 should provide the most potent antiinflammatory effects.
Weinberg
J B
JB
Duke University and  Medical Center, Durham, NC, USA. brice@acpub.duke.edu
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D051546:Cyclooxygenase 2; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D016898:Interferon-alpha / Q000494:pharmacology; D007527:Isoenzymes / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008565:Membrane Proteins; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D016898:Interferon-alpha; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases