Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on inflammatory cytokines expression

• GSNO modulates inflammatory processes, thus suggesting its potential use in therapy.
• Effects have been reported on a series of transcription factors and components of signal transduction chains.
• Results are not univocal and a single mechanism of action has not been identified.
• Controversies may be explained by cell type and experimental conditions adopted.

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.

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