Loss of the endothelial glucocorticoid receptor prevents the therapeutic protection afforded by dexamethasone after LPS.
Loss of the endothelial glucocorticoid receptor prevents the therapeutic protection afforded by dexamethasone after LPS.
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DOI：
10.1371/journal.pone.0108126
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sessa WC
中科院分区：
文献类型：
--
作者：
Goodwin JE;Feng Y;Velazquez H;Zhou H;Sessa WC
糖皮质激素通常被认为是多种疾病的抗炎治疗，并已成功用于治疗脓毒症和脓毒症样综合征。我们以前证明了内皮细胞中缺乏糖皮质激素受体的小鼠（GR EC KO小鼠）对低剂量LPS极其敏感，并证明了NF-κB的长期激活和上调。在这项研究中，我们用地塞米松预处理这些GR EC KO小鼠，并评估它们对相同剂量LPS的反应。令人惊讶的是，GR EC KO小鼠的表现甚至比单独给予LPS时更差，表明地塞米松预处理后死亡率增加、炎症细胞因子TNF-α和IL-6水平增加以及一氧化氮释放增加。正如预期的那样，用地塞米松预处理的对照动物显示出所有测定参数的改善。从机制上讲，我们证明，尽管使用地塞米松治疗，GR EC KO小鼠仍显示出iNOS产生和NF-κB活化增加。
Glucocorticoids are normally regarded as anti-inflammatory therapy for a wide variety of conditions and have been used with some success in treating sepsis and sepsis-like syndromes. We previously demonstrated that mice lacking the glucocorticoid receptor in the endothelium (GR EC KO mice) are extremely sensitive to low-dose LPS and demonstrate prolonged activation and up regulation of NF-κB. In this study we pre-treated these GR EC KO mice with dexamethasone and assessed their response to an identical dose of LPS. Surprisingly, the GR EC KO mice fared even worse than when given LPS alone demonstrating increased mortality, increased levels of the inflammatory cytokines TNF-α and IL-6 and increased nitric oxide release after the dexamethasone pre-treatment. As expected, control animals pre-treated with dexamethasone showed improvement in all parameters assayed. Mechanistically we demonstrate that GR EC KO mice show increased iNOS production and NF-κB activation despite treatment with dexamethasone.
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影响因子：
15.1
作者：
Guerrero, Julia;Gatica, Hector A.;Annelise Goecke, Irmgadt
通讯作者：
Annelise Goecke, Irmgadt
影响因子：
4.6
作者：
Haim YO;Unger ND;Souroujon MC;Mittelman M;Neumann D
通讯作者：
Neumann D
DOI：
10.1006/bbrc.1996.0115
发表时间：
1996-01-26
影响因子：
3.1
作者：
Kaddoura, S;Curzen, NP;PooleWilson, PA
通讯作者：
PooleWilson, PA
DOI：
10.1073/pnas.1222878110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Seok, Junhee;Warren, H. Shaw;Tompkins, Ronald G.
通讯作者：
Tompkins, Ronald G.
影响因子：
82.9
作者：
Lawrence, T;Gilroy, DW;Willoughby, DA
通讯作者：
Willoughby, DA