Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages.
Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages.
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茶碱恢复了COPD巨噬细胞中组蛋白脱乙酰基酶的活性和类固醇反应。
DOI：
10.1084/jem.20040416
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发表时间：
2004-09-06
影响因子：
15.3
通讯作者：
Barnes, PJ
中科院分区：
文献类型：
--
作者：
Cosio, BG;Tsaprouni, L;Ito, K;Jazrawi, E;Adcock, IM;Barnes, PJ
慢性阻塞性肺疾病（COPD）是一种常见的肺部慢性炎症性疾病，对糖皮质激素的反应很小或没有反应，氧化应激水平很高。组蛋白去乙酰化酶（HDAC）活性在吸烟者的细胞中降低，低浓度的茶碱可以增加HDAC活性。我们检测了茶碱对COPD患者肺泡巨噬细胞（AM）HDAC活性和炎症基因表达的影响。正常吸烟者AM HDAC活性较正常对照组降低，COPD患者AM HDAC活性降低51%（P < 0.01）。COPD AM还显示IL-8和TNF-α的基础释放增加，但地塞米松的抑制作用较差。茶碱诱导COPD AM裂解物中HDAC活性增加6倍，并显著增强地塞米松对诱导的IL-8释放的抑制，该作用可被HDAC抑制剂阿司他丁A阻断。因此，茶碱可能恢复COPD患者的类固醇反应性。
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.
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影响因子：
7.4
作者：
Täger, M;Piecyk, A;Welte, T
通讯作者：
Welte, T
影响因子：
4.8
作者：
Viatour, P;Legrand-Poels, S;Chariot, A
通讯作者：
Chariot, A
DOI：
10.1164/ajrccm.164.3.2007149
发表时间：
2001-08-01
影响因子：
24.7
作者：
Retamales, I;Elliott, WM;Hogg, JC
通讯作者：
Hogg, JC
DOI：
10.1164/rccm.200204-298oc
发表时间：
2003-01-01
影响因子：
24.7
作者：
Culpitt, SV;Rogers, DF;Barnes, PJ
通讯作者：
Barnes, PJ
DOI：
10.1016/j.bbrc.2004.01.046
发表时间：
2004-02-27
影响因子：
3.1
作者：
Ito, K;Hanazawa, T;Adcock, IM
通讯作者：
Adcock, IM