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Infect Immun 2007 Aug;75(8):3935-40

The large clostridial toxins from C. sordellii and C. difficile repress glucocorticoid receptor activity.

Tait AS, Dalton M, Geny B, D'Agnillo F, Popoff MR, Sternberg EM

Sternberg EM (reprint author), NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, 5625 Fishers Lane MSC 9401, Rockville, MD 20852 USA NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, Rockville, MD 20852 USA Inst Pasteur, Unite Bacteries Anaerobes & Toxines, Paris, France US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA


We have previously shown that Bacillus anthracis lethal toxin represses glucocorticoid receptor transactivation. We now report that repression of glucocorticoid receptor activity also occurs with the large clostridial toxins produced by C. 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 TNFalpha. Furthermore the glucocorticoid antagonist RU-486 in combination with C. sordellii lethal toxin additively prevented glucocorticoid suppression of TNFalpha. 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 MAPK.

Category: Journal Article
PubMed ID: #17517870
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29