Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

Sandra Camelo, Antonio H. Iglesias, Daehee Hwang, Brice Due, Hoon Ryu, Karen Smith, Steven G. Gray, Jaime Imitola, German Duran, Basel Assaf, Brett Langley, Samia J. Khoury, George Stephanopoulos, Umberto De Girolami, Rajiv R. Ratan, Robert J. Ferrante, Fernando Dangond

Research output: Contribution to journalArticle

226 Scopus citations

Abstract

We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.

Original languageEnglish (US)
Pages (from-to)10-21
Number of pages12
JournalJournal of Neuroimmunology
Volume164
Issue number1-2
DOIs
StatePublished - Jul 1 2005

Keywords

  • Experimental autoimmune encephalomyelitis
  • Histone deacetylase
  • Microarrays
  • Multiple sclerosis
  • Trichostatin A

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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    Camelo, S., Iglesias, A. H., Hwang, D., Due, B., Ryu, H., Smith, K., Gray, S. G., Imitola, J., Duran, G., Assaf, B., Langley, B., Khoury, S. J., Stephanopoulos, G., De Girolami, U., Ratan, R. R., Ferrante, R. J., & Dangond, F. (2005). Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 164(1-2), 10-21. https://doi.org/10.1016/j.jneuroim.2005.02.022