title: Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on inflammatory cytokines expression.
abstract: A number of experimental studies has documented that S-nitrosoglutathione (GSNO), the main endogenous low-molecular-weight S-nitrosothiol, can exert modulatory effects on inflammatory processes, thus supporting its potential employment in medicine for the treatment of important disease conditions. At molecular level, GSNO effects have been shown to modulate the activity of a series of transcription factors (notably NF-κB, AP-1, CREB and others) as well as other components of signal transduction chains (e.g. IKK-β, caspase 1, calpain and others), resulting in the modulation of several cytokines and chemokines expression (TNFα, IL-1β, IFN-γ, IL-4, IL-8, RANTES, MCP-1 and others). Results reported to date are however not univocal, and a single main mechanism of action for the observed anti-inflammatory effects of GSNO has not been identified. Conflicting observations can be explained by differences among the various cell types studies as to the relative abundance of enzymes in charge of GSNO metabolism (GSNO reductase, γ-glutamyltransferase, protein disulfide isomerase and others), as well as by variables associated with the individual experimental models employed. Altogether, anti-inflammatory properties of GSNO seem however to prevail, and exploration of the therapeutic potential of GSNO and analogues appears therefore warranted.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Italy. Electronic address: alessandro.corti@med.unipi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corti
authors.affiliation: Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy; Cardiology and Cardiovascular Medicine Division, Fondazione Toscana G. Monasterio - CNR, Pisa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Franzini
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Scataglini
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pompella
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D014157:Transcription Factors; D026422:S-Nitrosoglutathione; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; D005723:gamma-Glutamyltransferase; D019704:Protein Disulfide-Isomerases
keywords: Inflammation; Inflammatory cytokines; Nitric oxide; S-nitrosoglutathione; S-nitrosothiols; Signal transduction