来自索氏梭菌和艰难梭菌的大型梭菌毒素会抑制糖皮质激素受体活性。
The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity.
作者信息
Tait A Sasha, Dalton Monique, Geny Blandine, D'Agnillo Felice, Popoff Michel R, Sternberg Esther M
机构信息
Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health/NIH, 5625 Fishers Lane (MSC-9401), Rockville, MD 20852, USA.
出版信息
Infect Immun. 2007 Aug;75(8):3935-40. doi: 10.1128/IAI.00291-07. Epub 2007 May 21.
We have previously shown that Bacillus anthracis lethal toxin represses glucocorticoid receptor (GR) transactivation. We now report that repression of GR activity also occurs with the large clostridial toxins produced by Clostridium sordellii and C. difficile. This was demonstrated using a transient transfection assay system for GR transactivation. We also report that C. sordellii lethal toxin inhibited GR function in an ex vivo assay, where toxin reduced the dexamethasone suppression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Furthermore, the glucocorticoid antagonist RU-486 in combination with C. sordellii lethal toxin additively prevented glucocorticoid suppression of TNF-alpha. These findings corroborate the fact that GR is a target for the toxin and suggest a physiological role for toxin-associated GR repression in inflammation. Finally, we show that this repression is associated with toxins that inactivate p38 mitogen-activated protein kinase (MAPK).
我们之前已经表明，炭疽芽孢杆菌致死毒素可抑制糖皮质激素受体（GR）的反式激活。我们现在报告，索氏梭菌和艰难梭菌产生的大型梭菌毒素也会抑制GR活性。这是通过用于GR反式激活的瞬时转染分析系统来证明的。我们还报告，索氏梭菌致死毒素在体外分析中抑制GR功能，在该分析中，毒素降低了促炎细胞因子肿瘤坏死因子α（TNF-α）的地塞米松抑制作用。此外，糖皮质激素拮抗剂RU-486与索氏梭菌致死毒素联合使用可累加地阻止糖皮质激素对TNF-α的抑制作用。这些发现证实了GR是毒素的靶标这一事实，并提示毒素相关的GR抑制在炎症中具有生理作用。最后，我们表明这种抑制与使p38丝裂原活化蛋白激酶（MAPK）失活的毒素有关。
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