Regulation of the expression of inducible nitric oxide synthase.
Nitric oxide (NO), generated by the inducible isoform of nitric oxide synthase (iNOS), has been described to have beneficial microbicidal, antiviral, antiparasital, immunomodulatory, and antitumoral effects. However, aberrant iNOS induction at the wrong place or at the wrong time has detrimental consequences and seems to be involved in the pathophysiology of several human diseases. iNOS is primarily regulated at the expression level by transcriptional and post-transcriptional mechanisms. iNOS expression can be induced in many cell types with suitable agents such as bacterial lipopolysaccharides (LPS), cytokines, and other compounds. Pathways resulting in the induction of iNOS expression may vary in different cells or different species. Activation of the transcription factors NF-kappaB and STAT-1alpha, and thereby activation of the iNOS promoter, seems to be an essential step for iNOS induction in most cells. However, at least in the human system, also post-transcriptional mechanism are critically involved in the regulation of iNOS expression. The induction of iNOS can be inhibited by a wide variety of immunomodulatory compounds acting at the transcriptional levels and/or post-transcriptionally.
Kleinert
Hartmut
H
Department of Pharmacology, Johannes Gutenberg University, D-55101 Mainz, Germany.
Schwarz
Petra M
PM
Förstermann
Ulrich
U
D000818:Animals; D016207:Cytokines; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D016207:Cytokines; D050832:Interferon-Stimulated Gene Factor 3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; C079868:gamma interferon activation factor; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II