Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/96813
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dc.contributor.authorHodge, G.en
dc.contributor.authorJersmann, H.en
dc.contributor.authorTran, H.en
dc.contributor.authorRoscioli, E.en
dc.contributor.authorHolmes, M.en
dc.contributor.authorReynolds, P.en
dc.contributor.authorHodge, S.en
dc.date.issued2015en
dc.identifier.citationRespiratory Research, 2015; 16(1):130-1-130-11en
dc.identifier.issn1465-9921en
dc.identifier.issn1465-993Xen
dc.identifier.urihttp://hdl.handle.net/2440/96813-
dc.description.abstractHistone acetyltransferases (HAT) and histone deacetylases (HDAC) are enzymes that upregulate and down-regulate pro-inflammatory gene transcription respectively. HDAC2 is required by corticosteroids to switch off activated inflammatory genes and is reduced in lung macrophages in COPD. We have shown that COPD patients have increased steroid resistant CD28null (senescent) pro-inflammatory T and NKT-like peripheral blood cells (particularly CD8+ subsets) and we hypothesized that these changes would be associated with a loss of HDAC2 from these senescent pro-inflammatory lymphocytes.Blood was collected from 10 COPD and 10 aged-matched controls. Intracellular pro-inflammatory cytokines, IFNγ and TNFα, and expression of CD28, HDAC2 and HAT, were determined in lymphocyte subsets in the presence of ± 5 mg/ml theophylline (HDAC2 activator), 10 μM prednisolone and 2.5 ng/ml cyclosporine A (immunosuppressant), using flow cytometry.There was a loss of HDAC2 from CD28null CD8+ T and NKT-like cells in COPD. There was a significant negative correlation between HDAC2 expression and the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = -.763, p < 0.001 for T-cell IFNγ). There was a synergistic upregulation of HDAC2 and associated decrease in pro-inflammatory cytokine production in CD28nullCD8+ T and NKT-like cells in the presence of 5 mg/L theophylline + 10(-6) M prednisolone or 2.5 ng/mL cyclosporine A (CsA).Lymphocyte senescence in COPD is associated with loss of HDAC2 in CD28nullCD8+ T and NKT-like cells. Alternative treatment options such as combined theophylline with low-dose CsA, that inhibit these pro-inflammatory cells, may reduce systemic inflammation in COPD.en
dc.description.statementofresponsibilityGreg Hodge, Hubertus Jersmann, Hai B. Tran, Eugene Roscioli, Mark Holmes, Paul N. Reynolds and Sandra Hodgeen
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rights© 2015 Hodge et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectLymphocyte senescence; COPD; HDAC2; CD28nullCD8+ T and NKT-like cells; IFNγ and TNFαen
dc.titleLymphocyte senescence in COPD is associated with decreased histone deacetylase 2 expression by pro-inflammatory lymphocytesen
dc.typeJournal articleen
dc.identifier.doi10.1186/s12931-015-0287-2en
pubs.publication-statusPublisheden
dc.identifier.orcidJersmann, H. [0000-0003-1763-2736]en
dc.identifier.orcidTran, H. [0000-0002-9463-4033]en
dc.identifier.orcidRoscioli, E. [0000-0002-3201-3899]en
dc.identifier.orcidReynolds, P. [0000-0002-2273-1774]en
dc.identifier.orcidHodge, S. [0000-0002-3602-9927]en
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