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- Title
The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ.
- Authors
Hashioka, Sadayuki; Klegeris, Andis; McGeer, Patrick L
- Abstract
<bold>Backgrounds: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Publication
Journal of Neuroinflammation, 2012, Vol 9, Issue 1, p113
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/1742-2094-9-113