Histone deacetylase inhibitors suppress immune activation in primary mouse microglia

Vishnu Kannan, Nieske Brouwer, Uwe-Karsten Hanisch, Tommy Regen, Bart J. L. Eggen*, Hendrikus W. G. M. Boddeke

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

Abstract

Neuroinflammation is required for tissue clearance and repair after infections or insults. To prevent excessive damage, it is crucial to limit the extent of neuroinflammation and thereby the activation of its principal effector cell, microglia. The two main major innate immune cell types in the CNS are astrocytes and microglia. Histone deacetylases (HDACs) have been implicated in regulating the innate inflammatory response, and here we addressed their role in pure astrocyte and microglia cultures. Endogenous HDAC expression levels were determined in microglia and astrocytes and after treatment with lipopolysaccharide (LPS) or LPS and interferon (IFN). The relative expression level of HDACs was reduced in LPS- or LPS/IFN (with the exception of HDAC1 and -7)-stimulated astrocytes and increased in microglia after LPS treatment both in primary cultures and in microglia acutely isolated from LPS-treated mice, so we focused on the inflammatory response in microglia. Primary microglia cultures were treated with LPS in the presence or absence of HDAC inhibitors (HDACi). Expression and release of inflammatory cytokines was determined by quantitative RT-PCR, flow cytometry, and ELISA. HDACi strongly suppressed LPS-induced cytokine expression and release by microglia. Furthermore, expression of M1- and M2-associated activation markers was suppressed, and the migratory behavior of microglia was attenuated. Our findings strongly suggest that HDACi suppress innate immune activation in microglia. (c) 2013 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)1133-1142
Number of pages10
JournalJournal of Neuroscience Research
Volume91
Issue number9
DOIs
Publication statusPublished - Sep-2013

Keywords

  • primary microglia and astrocytes
  • lipopolysaccharide
  • M1-M2 activation markers
  • innate immunity
  • PROINFLAMMATORY GENE-EXPRESSION
  • SUBEROYLANILIDE HYDROXAMIC ACID
  • INFLAMMATORY RESPONSE
  • BRAIN-INJURY
  • IFN-GAMMA
  • IN-VIVO
  • LIPOPOLYSACCHARIDE
  • CELLS
  • ASTROCYTES
  • LPS

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