Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages.
Article Details
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Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ
Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages.
J Exp Med. 2004 Sep 6;200(5):689-95. Epub 2004 Aug 30.
- PubMed ID
- 15337792 [ View in PubMed]
- Abstract
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-alpha, 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Oxtriphylline Histone deacetylase 2 Protein Humans YesActivatorDetails Theophylline Histone deacetylase 2 Protein Humans YesActivatorDetails