Inducible Nitric Oxide Synthase Binds, S-Nitrosylates, and Activates Cyclooxygenase-2

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Here we show that iNOS specifically binds to COX-2 and S-nitrosylates it, enhancing COX-2 catalytic activity. Selectively disrupting iNOS–COX-2 binding prevented NO-mediated activation of COX-2. This synergistic molecular interaction between two inflammatory systems may inform the development of anti-inflammatory drugs.