Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation

Nitric oxide (NO) and prostaglandin (PG) E-2 produced by NO synthase type 2 (NOS2) and cyclooxygenase type 2 (COX2), respectively, are important media tors in inflammation. There is much information regarding their roles in mo dels of inflammation in mice and in humans with diseases such as rheumatoid arthritis (RA). A variety of stimuli including cytokines, microbial compon ents, immune complexes, and mechanical stress can induce both NOS2 and COX2 mRNA transcription and protein synthesis and enhance inflammation. This ha s been demonstrated in both mice and humans. NOS2-specific inhibitors reduc e inflammation in mice, and COX2-specific inhibitors reduce inflammation in mice and in humans. There is significant cross-talk between PGE(2)/NO and COX2/NOS2. Treatments that inhibit both NOS2 and COX2 should provide the mo st potent antiinflammatory effects.