Durham, BS, Grigg, R and Wood, IC orcid.org/0000-0003-1886-2533 (2017) Inhibition of histone deacetylase 1 or 2 reduces induced cytokine expression in microglia through a protein synthesis independent mechanism. Journal of Neurochemistry, 143 (2). pp. 214-224. ISSN 0022-3042
Abstract
Histone deacetylase (HDAC) inhibitors prevent neural cell death in in vivo models of cerebral ischaemia, brain injury and neurodegenerative disease. One mechanism by which HDAC inhibitors may do this is by suppressing the excessive inflammatory response of chronically activated microglia. However, the molecular mechanisms underlying this anti-inflammatory effect and the specific HDAC responsible are not fully understood. Recent data from in vivo rodent studies has shown that inhibition of class I HDACs suppresses neuroinflammation and is neuroprotective. In our study we have identified that selective HDAC inhibition with inhibitors apicidin, MS-275 or MI-192, or specific knockdown of HDAC1 or 2 using siRNA, suppresses the expression of cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in BV2 murine microglia activated with lipopolysaccharide (LPS). Furthermore, we found that in the absence of HDAC1, HDAC2 is upregulated and these increased levels are compensatory, suggesting these two HDACs have redundancy in regulating the inflammatory response of microglia. Investigating the possible underlying anti-inflammatory mechanisms suggests an increase in protein expression is not important. Taken together, this study supports the idea that inhibitors selective towards HDAC1 or HDAC2, may be therapeutically useful for targeting neuroinflammation in brain injuries and neurodegenerative disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 International Society for Neurochemistry. This is the peer reviewed version of the following article: Durham, B. S., Grigg, R. and Wood, I. C. (2017), Inhibition of histone deacetylase 1 or 2 reduces induced cytokine expression in microglia through a protein synthesis independent mechanism. Journal of Neurochemistry. doi:10.1111/jnc.14144, which has been published in final form at https://doi.org/10.1111/jnc.14144. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | acetylation; gene expression; HDAC; microglia |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 Aug 2017 09:28 |
Last Modified: | 12 Feb 2019 17:17 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/jnc.14144 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119679 |