Yersinia enterocolitica YopT and Clostridium difficile toxin B induce expression of GILZ in epithelial cells

Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype Yersinia en...

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Bibliographic Details
Published in:PloS one 2012-07, Vol.7 (7), p.e40730-e40730
Main Authors: Köberle, Martin, Göppel, David, Grandl, Tanja, Gaentzsch, Peer, Manncke, Birgit, Berchtold, Susanne, Müller, Steffen, Lüscher, Bernhard, Asselin-Labat, Marie-Liesse, Pallardy, Marc, Sorg, Isabel, Langer, Simon, Barth, Holger, Zumbihl, Robert, Autenrieth, Ingo B, Bohn, Erwin
Format: Article
Language:English
Subjects:
Activation
Anti-inflammatory agents
Antigens
Apoptosis
Bacteria
Bacterial Proteins - metabolism
Bacterial Toxins - metabolism
Base Sequence
Binding sites
Biology
c-Myc protein
Cysteine Endopeptidases - metabolism
Cytokines
Deactivation
Dendritic cells
Deprivation
Dexamethasone
DNA binding proteins
E-Box Elements
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - microbiology
Experiments
Flow cytometry
G proteins
Gene Expression
Gene Expression Profiling
Glucocorticoids
Guanosine triphosphatases
Guanosinetriphosphatase
Health aspects
HeLa Cells
Humans
Inactivation
Infection
Infections
Inflammation
Inflammation - genetics
Inflammation Mediators - metabolism
Interleukin 10
Interleukin 2
Leucine
Leucine zipper proteins
Life Sciences
MAP kinase
Medical research
Medicine
Mitogen-Activated Protein Kinases - metabolism
Myc protein
NF-kappa B - metabolism
Promoter Regions, Genetic
Proteases
Protein expression
Proteins
rho GTP-Binding Proteins - metabolism
RhoA protein
RNA
Signal Transduction
Signaling
Toxicology
Toxin B
Toxins
Transcription
Transcription Factors - genetics
Transcription, Genetic
Transcriptional Activation
Upstream stimulating factor 1
Upstream stimulating factor 2
Upstream stimulatory factor
Upstream Stimulatory Factors - metabolism
Yersinia
Yersinia enterocolitica
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Summary:Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype Yersinia enterocolitica which carry the pYV plasmid upregulated GILZ mRNA levels and protein expression in epithelial cells. Infection of HeLa cells with different Yersinia mutant strains revealed that the protease activity of YopT, which cleaves the membrane-bound form of Rho GTPases was sufficient to induce GILZ expression. Similarly, Clostridium difficile toxin B, another bacterial inhibitor of Rho GTPases induced GILZ expression. YopT and toxin B both increased transcriptional activity of the GILZ promoter in HeLa cells. GILZ expression could not be linked to the inactivation of an individual Rho GTPase by these toxins. However, forced expression of RhoA and RhoB decreased basal GILZ promoter activity. Furthermore, MAPK activation proved necessary for profound GILZ induction by toxin B. Promoter studies and gel shift analyses defined binding of upstream stimulatory factor (USF) 1 and 2 to a canonical c-Myc binding site (E-box) in the GILZ promoter as a crucial step of its trans-activation. In addition we could show that USF-1 and USF-2 are essential for basal as well as toxin B induced GILZ expression. These findings define a novel way of GILZ promoter trans-activation mediated by bacterial toxins and differentiate it from those mediated by dexamethasone or deprivation of IL-2.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0040730