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

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-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).

journal_name

Infect Immun

journal_title

Infection and immunity

authors

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

doi

10.1128/IAI.00291-07

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

3935-40

issue

8

eissn

0019-9567

issn

1098-5522

pii

IAI.00291-07

journal_volume

75

pub_type

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