The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity.
The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity.
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来自索氏梭菌和艰难梭菌的大梭菌毒素可抑制糖皮质激素受体活性。
DOI：
10.1128/iai.00291-07
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发表时间：
2007
影响因子：
3.1
通讯作者：
Sternberg,EstherM
中科院分区：
文献类型：
--
作者：
Tait,ASasha;Dalton,Monique;Geny,Blandine;D'Agnillo,Felice;Popoff,MichelR;Sternberg,EstherM
我们先前已经证明炭疽杆菌致死毒素抑制糖皮质激素受体（GR）的反式激活。我们现在报告GR活性的抑制也发生在梭菌产生的大梭菌毒素中。很难这是证明使用GR反式激活的瞬时转染测定系统。我们还报告说，C。在离体试验中，sordelliilethal毒素抑制GR功能，其中毒素减少地塞米松对促炎细胞因子肿瘤坏死因子α（TNF-α）的抑制。此外，糖皮质激素拮抗剂RU-486与C.蛙毒素可增加糖皮质激素对TNF-α的抑制作用。这些发现证实了GR是毒素的靶点，并表明毒素相关的GR抑制在炎症中的生理作用。最后，我们表明，这种抑制与毒素，p38丝裂原活化蛋白激酶（MAPK）。
We have previously shown thatBacillus anthracislethal toxin represses glucocorticoid receptor (GR) transactivation. We now report that repression of GR activity also occurs with the large clostridial toxins produced byClostridium sordelliiandC. difficile. This was demonstrated using a transient transfection assay system for GR transactivation. We also report thatC. sordelliilethal toxin inhibited GR function in an ex vivo assay, where toxin reduced the dexamethasone suppression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). Furthermore, the glucocorticoid antagonist RU-486 in combination withC. sordelliilethal toxin additively prevented glucocorticoid suppression of TNF-α. 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).