Cross-talk between constitutive and inducible NO synthase: an update

Inducible nitric oxide synthase (iNOS) is expressed upon exposure of some cell types to bacterial lipopolysaccharides (LPS) and/or a variety of proinflammatory cytokines. The authors present an overview of some of the recent findings further supporting the notion that this response takes place after an early decline in constitutive nitric oxide (NO) levels (i.e., NO released by constitutive NOS, cNOS). This response is indeed critical for allowing activation of the transcription factor NF-kappaB. Thus, generation of NO by cNOS represents a limiting factor for iNOS expression. Some of the physiological and pathological implications of the cross-talk between these two NOS isoforms are discussed. In addition, the results of recent studies are summarized, suggesting possible mechanisms whereby LPS and/or proinflammatory cytokines may cause inhibition of cNOS.