Endogenous Glucocorticoids Inhibit Myocardial Inflammation Induced by Lipopolysaccharide: Involvement of Regulation of Histone Deacetylation
Endogenous Glucocorticoids Inhibit Myocardial Inflammation Induced by Lipopolysaccharide: Involvement of Regulation of Histone Deacetylation
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内源性糖皮质激素抑制脂多糖诱导的心肌炎症：参与组蛋白脱乙酰化的调节
DOI：
10.1097/fjc.0b013e3182567fef
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发表时间：
2012-07
影响因子：
3
通讯作者：
Chen, Min-Sheng
中科院分区：
文献类型：
--
作者：
Wu, Xiao-qian;Liu, Shi-Ming;Luo, Jian-Dong;Chen, Min-Sheng
翻译后摘要：新出现的证据表明，心肌炎症在心脏疾病的发病机制中起着关键作用。但这种慢性炎症性疾病的确切机制尚未阐明。糖皮质激素（GC）是可用于许多炎性疾病的最有效的抗炎治疗。然而，内源性GC是否能够对心肌炎症发挥抗炎作用尚不清楚。在这项研究中，内源性GCs在心肌炎症调节中的潜在作用进行了研究。我们发现，肾上腺切除术降低内源性GC水平促进了基础和脂多糖（LPS）诱导的促炎细胞因子的产生，补充外源性生理水平的氢化可的松可以部分逆转。GC受体（GR）拮抗剂米非司酮（RU 486）或组蛋白去乙酰化酶抑制剂阿司他丁A（TSA）抑制GR信号通路也增加了基础和LPS诱导的促炎细胞因子的水平。此外，阻断GC-GR信号通路的肾上腺切除，RU 486或TSA增强LPS诱导的心肌核因子-B活化和组蛋白乙酰化，但抑制心肌组蛋白去乙酰化酶的表达和活性。心功能研究表明，阻断GC-GR信号通路可加重炎症诱导的心功能障碍。这些结果表明，内源性GCs能够抑制LPS诱导的心肌炎症。内源性GCs是大鼠心肌重要的内源性抗炎机制，这种机制的损伤可能是心脏疾病发病的重要因素。
Abstract: Emerging evidence indicates that myocardial inflammation plays a key role in the pathogenesis of cardiac diseases. But the exact mechanisms for this chronic inflammatory disorder have not been elucidated. Glucocorticoids (GCs) are the most effective anti-inflammatory treatments available for many inflammatory diseases. However, it is unknown whether endogenous GCs are able to exert anti-inflammatory effect on myocardial inflammation. In this study, the potential role of endogenous GCs in the regulation of myocardial inflammation was investigated. We showed that the reduction of endogenous GC level by adrenalectomy promoted the production of basal and lipopolysaccharide (LPS)-induced proinflammatory cytokines, which could be partly reversed by supplementing with exogenous physiological level of hydrocortisone. Inhibition of GC receptor (GR) signaling pathway with GR antagonist mifepristone (RU486) or histone deacetylase inhibitor trichostatin A (TSA) also increased the levels of basal and LPS-induced proinflammatory cytokines. Moreover, blockade of GC–GR signaling pathway by adrenalectomy, RU486 or TSA enhanced LPS-induced myocardial nuclear factor-&kgr;B activation and histone acetylation but inhibited myocardial histone deacetylase expression and activity. Cardiac function studies demonstrated that blockade of the GC–GR signaling pathway aggravated inflammation-induced cardiac dysfunction. These findings indicate that endogenous GCs are able to inhibit myocardial inflammation induced by LPS. Endogenous GCs represent an important endogenous anti-inflammatory mechanism for myocardium in rats and such mechanism injury may be an important factor for pathogenesis of cardiac diseases.
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DOI：
--
发表时间：
2004
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
F. M. Moodie;John A. Marwick;Charlotte S Anderson;P. Szulakowski;S. Biswas;M. Bauter;I. Kilty;I. Rahman
通讯作者：
F. M. Moodie;John A. Marwick;Charlotte S Anderson;P. Szulakowski;S. Biswas;M. Bauter;I. Kilty;I. Rahman
组蛋白脱乙酰基酶2介导的糖皮质激素受体的脱乙酰基化可以抑制NF-kappab。
影响因子：
15.3
作者：
Ito, Kazuhiro;Yamamura, Satoshi;Essilfie-Quaye, Sarah;Cosio, Borja;Ito, Misako;Barnes, Peter J;Adcock, Ian M
通讯作者：
Adcock, Ian M
影响因子：
3
作者：
Yu Y;Wan Y;Huang C
通讯作者：
Huang C
影响因子：
5.8
作者：
Rahman, I;Marwick, J;Kirkham, P
通讯作者：
Kirkham, P
影响因子：
4.8
作者：
Moodie, FM;Marwick, JA;Rahman, I
通讯作者：
Rahman, I