The Large Clostridial Toxins from Clostridium sordellii and C. difficile Repress Glucocorticoid Receptor Activity
- 1 August 2007
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 75 (8) , 3935-3940
- https://doi.org/10.1128/iai.00291-07
Abstract
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-α). Furthermore, the glucocorticoid antagonist RU-486 in combination with C. 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).Keywords
This publication has 33 references indexed in Scilit:
- Clinical Features ofClostridium difficile–Associated Infections and Molecular Characterization of Strains: Results of a Retrospective Study, 2000-2004Infection Control & Hospital Epidemiology, 2007
- Yersinia YopJ Acetylates and Inhibits Kinase Activation by Blocking PhosphorylationScience, 2006
- Endocrine Perturbation Increases Susceptibility of Mice to Anthrax Lethal ToxinInfection and Immunity, 2005
- Anthrax lethal toxin represses glucocorticoid receptor (GR) transactivation by inhibiting GR-DNA binding in vivoMolecular and Cellular Endocrinology, 2005
- Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPKJournal of Biological Chemistry, 2005
- Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral productsJournal of Endocrinology, 2004
- Anthrax Edema Toxin Requires Influx of Calcium for Inducing Cyclic AMP Toxicity in Target CellsInfection and Immunity, 2002
- p38 MAP kinase activation by Clostridium difficile toxin A mediates monocyte necrosis, IL-8 production, and enteritisJournal of Clinical Investigation, 2000
- Ras, Rap, and Rac Small GTP-binding Proteins Are Targets for Clostridium sordellii Lethal Toxin GlucosylationJournal of Biological Chemistry, 1996
- Effect of diphtheria toxin on protein synthesis: Inactivation of one of the transfer factorsJournal of Molecular Biology, 1967