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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Aging and peripheral lipopolysaccharide can modulate epigenetic regulators and decrease IL-1 beta promoter DNA methylation in microglia
Neurobiology of aging, v 47, pp 1-9
01 Nov 2016
PMID: 27500965
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In aged mice, peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes exaggerated neuroinflammation and prolonged sickness behavior due in part to microglial dysfunction. Epigenetic changes to DNA may play a role in microglial dysfunction; therefore, we sought to determine whether aged microglia displayed DNA hypomethylation of the interleukin-1 beta (IL-1 beta) promoter and altered expression of epigenetic regulators. We further examined whether the demethylating agent 5-azacytidine induced IL-1 beta expression in BV2 and primary microglia similar to microglia from aged mice. Novel findings indicated that aged mice had decreased methylation of the IL-1 beta gene promoter in primary microglia basally or following systemic LPS that is associated with increased IL-1 beta mRNA, intracellular IL-1 beta production, as well as prolonged sickness behavior. Last, 5-azacytidine increased IL-1 beta gene expression and decreased DNA methylation of BV2 and primary microglial cells similar to microglia from aged mice. Taken together, these data indicate that DNA methylation promotes heightened microglial activation in the aged brain. (C) 2016 Elsevier Inc. All rights reserved.
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Details
- Title
- Aging and peripheral lipopolysaccharide can modulate epigenetic regulators and decrease IL-1 beta promoter DNA methylation in microglia
- Creators
- Stephanie M. Matt - University of Illinois Urbana-ChampaignMarcus A. Lawson - University of Illinois Urbana-ChampaignRodney W. Johnson - University of Illinois Urbana-Champaign
- Publication Details
- Neurobiology of aging, v 47, pp 1-9
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- R01 AG16710 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AG016710 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000386976500001
- Scopus ID
- 2-s2.0-84982733749
- Other Identifier
- 991021902597004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Geriatrics & Gerontology
- Neurosciences