Open AccessThe Large Clostridial Toxins from Clostridium sordellii and C. difficile Repress Glucocorticoid Receptor Activity
Author(s) -
A. Sasha Tait,
Monique Dalton,
Blandine Geny,
Felice D’Agnillo,
Michel R. Popoff,
Esther M. Sternberg
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00291-07
Subject(s) - biology , glucocorticoid receptor , transactivation , microbiology and biotechnology , glucocorticoid , clostridium difficile toxin a , clostridium difficile toxin b , proinflammatory cytokine , anthrax toxin , toxin , immunology , clostridium difficile , inflammation , transcription factor , biochemistry , fusion protein , gene , recombinant dna , antibiotics
We have previously shown thatBacillus anthracis lethal toxin represses glucocorticoid receptor (GR) transactivation. We now report that repression of GR activity also occurs with the large clostridial toxins produced byClostridium sordellii andC. difficile . This was demonstrated using a transient transfection assay system for GR transactivation. We also report thatC. 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-α). Furthermore, the glucocorticoid antagonist RU-486 in combination withC. sordellii lethal 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).