Regulation of the inducible nitric oxide synthase (iNOS) gene

Induced nitric oxide (NO), the end product of the enzyme inducible nitric oxide synthase (iNOS), has been shown to be an important mediator in a number of human diseases and cancers [1–4]. L-arginine is converted to the NO and L-citrulline by the inducible isoform of nitric oxide synthase and produces high levels of NO (Fig. 1). Once produced, NO has a short half-life (t1/2 = s) and undergoes spontaneous oxidation to the inactive metabolites nitrite and nitrate (NO2 - and NO3 -). Because iNOS is involved in the pathogenesis of the inflammatory response, the characterization of the cis- and trans-activating factors which regulate lipopolysacharide-(LPS) and cytokine-induced iNOS expression have been pursued. This review will summarize and contrast the molecular regulation of the murine and human iNOS genes. The regulation of iNOS is complex and occurs at multiple sites within the signal transduction pathways that lead to iNOS gene expression and includes transcription and post-transcriptional mechanisms of modification.