Cited by 86Neuroinflammation and Neurodegeneration MechanismsHistone Deacetylase Inhibitors ResearchImmune Response and Inflammation

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

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Suh, Hyeon-Sook, Choi, Shinyeop, Khattar, Pallavi, Choi, Namjong, Lee, Sunhee C.·2010·Journal of Neuroimmune Pharmacology

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.

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  • HDAC inhibitors exert neuroprotective effects through anti-inflammatory mechanisms such as reduced microglial activation and through non-transcriptional actions including microtubule acetylation-mediated support of axonal transport and plasticity.

    “HDAC inhibitors exert neuroprotective effects through both anti-inflammatory mechanisms, such as reduced microglial activation, and non-transcriptional actions, including microtubule acetylation–mediated support of axonal transport and plasticity (Glozak et al., 2005; Chuang et al., 2009; Suh et al., 2010).”

    From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Suh et al., 2010

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Authors
Suh, H.-S., Choi, S., Khattar, P., Choi, N., & Lee, S. C.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Lee, Sunhee C.
Venue
Journal of Neuroimmune Pharmacology
Published
2010-02-17
Volume
5
Issue
4
Pages
521-532
ISSN
  • 1557-1890 (ISSN-L)
  • 1557-1904
OpenAlex
W2047558881
Cited by
86
References
49
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 2 · 2013: 10 · 2012: 6
FWCI
3.48
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroimmune Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Albert Einstein College of Medicine, Yeshiva University
  • National Institute of Mental Health (R01MH055477, R01 MH 55477, K01MH084705)
  • National Institute of Allergy and Infectious Diseases (P30AI051519)
  • National Institute of Neurological Disorders and Stroke (T32NS007098)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
histone deacetylase inhibitors, trichostatin A, valproic acid, microglia, astrocytes, antiviral innate immunity, interferon-beta, interferon-stimulated genes, TLR3 signaling, TLR4 signaling, cytokine gene expression, chemokine expression, neuroinflammation
MeSH terms
Astrocytes, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Hydroxamic Acids, Immunity, Innate, Inflammation, Valproic Acid, Blotting, Western, Gene Expression, Cytokines, Microglia, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Histone Deacetylase Inhibitors

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