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

Journal of Neuroinflammation

Patrick L McGeer³  Andis Klegeris²  Sadayuki Hashioka¹ 

[1] Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidasi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan;Department of Biology, I.K. Barber School of Arts and Sciences, the University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, V1V 1 V7, Canada;Kinsmen Laboratory of Neurological Research, Department of Psychiatry, the University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada

关键词: Neurodegenerative diseases;    Neuroinflammation;    Astrocytes;    I-TAC;    STAT3;    SAHA;    HDAC inhibitor;   

Others  :  1212563
DOI  :  10.1186/1742-2094-9-113

 received in 2012-03-01, accepted in 2012-05-30,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Hashioka et al.; licensee BioMed Central Ltd.

【 图 表 】

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