Gowers, I.R., Walters, K., Kiss-Toth, E. et al. (3 more authors) (2011) Age-related loss of CpG methylation in the tumour necrosis factor promoter. Cytokine, 56 (3). pp. 792-797. ISSN 1043-4666
Abstract
Background: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines. Methylation of DNA is an important regulator of gene expression and changes with age.
Objective: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leucocytes and macrophages.
Methods and results: Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) in the TNF promoter in human peripheral blood cells from 312 healthy controls (0.8% per decade, confidence interval (CI) = 0.44-1.13%, p = 1 x 10(-5)) and primary monocyte-derived macrophages (MDM) from a separate population of 78 healthy controls (1.4% per decade, CI = 0.79-2.13%, p = 7 x 10(-5)). Methylation a TNF promoter fragment (-345-+154) resulted in 78% reduction of reporter gene activity compared with the unmethylated promoter construct.
Conclusions: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator. (C) 2011 Elsevier Ltd. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2011 Elsevier. This is an author produced version of a paper subsequently published in Cytokine. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | DNA methylation; Age; TNF; Expression; Epigenetics |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Department of Infection & Immunity |
Depositing User: | Miss Anthea Tucker |
Date Deposited: | 27 Jan 2012 15:30 |
Last Modified: | 08 Feb 2013 17:36 |
Published Version: | http://dx.doi.org/10.1016/j.cyto.2011.09.009 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.cyto.2011.09.009 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:43687 |