Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes

Hyeon Sook Suh, Shinyeop Choi, Pallavi Khattar, Namjong Choi, Sunhee C. Lee

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Histone deacetylase inhibitors (HDACi) have been proposed as therapies for certain cancers and as an anti-reservoir therapy for HIV+ individuals with highly active anti-retroviral therapy, yet their roles in glial inflammatory and innate antiviral gene expression have not been defined. In this study, we examined the effects of two non-selective HDACi, trichostatin A and valproic acid, on antiviral and cytokine gene expression in primary human microglia and astrocytes stimulated with TLR3 or TLR4 ligand. HDACi potently suppressed the expression of innate antiviral molecules such as IFNβ, interferon-simulated genes, and proteins involved in TLR3/TLR4 signaling. HDACi also suppressed microglial and astrocytic cytokine and chemokine gene expression, but with different effects on different groups of cytokines. These results have important implications for the clinical use of HDACi.

Original languageEnglish (US)
Pages (from-to)521-532
Number of pages12
JournalJournal of Neuroimmune Pharmacology
Volume5
Issue number4
DOIs
Publication statusPublished - Dec 1 2010

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Keywords

  • HIV
  • TLR
  • astrocytes
  • cytokines
  • histone deacetylase
  • innate immunity
  • microglia
  • valproic acid

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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