Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages

Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline...

Full description

Bibliographic Details
Main Authors: Cosio, Borja G., Tsaprouni, Loukia, Ito, Kazuhiro, Jazrawi, Elen, Adcock, Ian M., Barnes, Peter J.
Format: Online
Language:English
Published: The Rockefeller University Press 2004
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212744/
id pubmed-2212744
recordtype oai_dc
spelling pubmed-22127442008-03-11 Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages Cosio, Borja G. Tsaprouni, Loukia Ito, Kazuhiro Jazrawi, Elen Adcock, Ian M. Barnes, Peter J. Brief Definitive Report Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P < 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients. The Rockefeller University Press 2004-09-06 /pmc/articles/PMC2212744/ /pubmed/15337792 http://dx.doi.org/10.1084/jem.20040416 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Cosio, Borja G.
Tsaprouni, Loukia
Ito, Kazuhiro
Jazrawi, Elen
Adcock, Ian M.
Barnes, Peter J.
spellingShingle Cosio, Borja G.
Tsaprouni, Loukia
Ito, Kazuhiro
Jazrawi, Elen
Adcock, Ian M.
Barnes, Peter J.
Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
author_facet Cosio, Borja G.
Tsaprouni, Loukia
Ito, Kazuhiro
Jazrawi, Elen
Adcock, Ian M.
Barnes, Peter J.
author_sort Cosio, Borja G.
title Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
title_short Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
title_full Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
title_fullStr Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
title_full_unstemmed Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages
title_sort theophylline restores histone deacetylase activity and steroid responses in copd macrophages
description Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P < 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients.
publisher The Rockefeller University Press
publishDate 2004
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212744/
_version_ 1611434349747503104

Similar Items