Inflammatory mechanisms interact

Two mechanisms known to be involved in inflammation are the production of nitric oxide by the enzyme inducible nitric oxide synthase (iNOS) and the formation of prostaglandins by cyclooxygenase-2 (COX-2). COX-2 inhibitors are used as anti-inflammatory agents, but they have come under fire recently. Solomon H. Snyder, Sangwon F. Kim, and Daniel A. Huri at Johns Hopkins University School of Medicine now show that iNOS binds to COX-2 and S-nitrosylates it on one of its cysteine residues, increasing the catalytic activity of COX-2 (Science 2005, 310, 1966). Disrupting the interaction between the two enzymes prevents NO-mediated activation of COX-2. The authors suggest that preventing this interaction is a possible therapeutic avenue that would be synergistic with COX-2 inhibitors, allowing smaller doses to be used.