Journal of Neuroimmune Pharmacology

, Volume 5, Issue 4, pp 521–532

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
ORIGINAL ARTICLE

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.

Keywords

histone deacetylase microglia cytokines innate immunity HIV astrocytes valproic acid TLR 

Abbreviations

HDAC

Histone deacetylase

HDACi

HDAC inhibitor

IFNAR

Type I interferon receptor

ISRE

IFN-stimulated response element

PIC (poly I:C)

Polyinosinic–polycytidylic acid

PBDA

Porphobilinogen deaminase

Q-PCR

Real-time RT–PCR

VA

Valproic acid

IDO

Indoleamine 2, 3-dioxygenase

IRF

Interferon regulatory factor

ISGs

IFN-stimulated genes

LPS

Lipopolysaccharide

TLR

Toll-like receptor

TRIF

Toll/interleukin-1 receptor domain-containing adaptor protein inducing IFNβ

TSA

Trichostatin A

Supplementary material

11481_2010_9192_MOESM1_ESM.xls (441 kb)
ESM(XLS 441 KB)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Hyeon-Sook Suh
    • 1
  • Shinyeop Choi
    • 1
  • Pallavi Khattar
    • 1
  • Namjong Choi
    • 1
  • Sunhee C. Lee
    • 1
  1. 1.Department of PathologyAlbert Einstein College of MedicineBronxUSA

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