The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ

Backgrounds: increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (saha) possesses potent anti-inflammatory and immunomodulatory properties. it is tempting to evaluate the potential of saha as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders.methods: we examined the effects of saha on interferon (ifn)-γ-induced neurotoxicity of human astrocytes and on ifn-γ-induced phosphorylation of signal transducer and activator of transcription (stat) 3 in human astrocytes. we also studied the effects of saha on the astrocytic production of two representative ifn-γ-inducible inflammatory molecules,namely ifn-γ-inducible t cell α chemoattractant (i-tac) and intercellular adhesion molecule-1 (icam-1).results: saha significantly attenuated the toxicity of astrocytes activated by ifn-γ towards sh-sy5y human neuronal cells. in the ifn-γ-activated astrocytes,saha reduced the stat3 phosphorylation. saha also inhibited the ifn-γ-induced astrocytic production of i-tac,but not icam-1. these results indicate that saha suppresses ifn-γ-induced neurotoxicity of human astrocytes through inhibition of the stat3 signaling pathway.conclusion: due to its anti-neurotoxic and anti-inflammatory properties,saha appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes. © 2012 hashioka et al.; licensee biomed central ltd.