Abstract | BACKGROUND: METHODS/PRINCIPAL FINDINGS: We hypothesized that Salmonella elevates the leaky protein claudin-2 for its own benefit to facilitate bacterial invasion in the colon. Using a Salmonella- colitis mouse model and cultured colonic epithelial cells, we found that pathogenic Salmonella colonization significantly increases the levels of claudin-2 protein and mRNA in the intestine, but not that of claudin-3 or claudin-7 in the colon, in a time-dependent manner. Immunostaining studies showed that the claudin-2 expression along the crypt-villous axis postinfection. In vitro, Salmonella stimulated claudin-2 expression in the human intestinal epithelial cell lines SKCO15 and HT29C19A. Further analysis by siRNA knockdown revealed that claudin-2 is associated with the Salmonella-induced elevation of cell permeability. Epithelial cells with claudin-2 knockdown had significantly less internalized Salmonella than control cells with normal claudin-2 expression. Inhibitor assays demonstrated that this regulation is mediated through activation of the EGFR pathway and the downstream protein JNK. CONCLUSION/SIGNIFICANCE: We have shown that Salmonella targets the tight junction protein claudin-2 to facilitate bacterial invasion. We speculate that this disruption of barrier function contributes to a new mechanism by which bacteria interact with their host cells and suggests the possibility of blocking claudin-2 as a potential therapeutic strategy to prevent bacterial invasion.
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Authors | Yong-guo Zhang, Shaoping Wu, Yinglin Xia, Jun Sun |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 3
Pg. e58606
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23505542
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Cell Line
- Claudin-2
(genetics, metabolism)
- Colon
(metabolism, microbiology)
- Epithelial Cells
(metabolism)
- Female
- Gene Expression Regulation
- Humans
- Intestinal Mucosa
(metabolism)
- MAP Kinase Signaling System
- Mice
- Permeability
- Salmonella Infections
(genetics, metabolism)
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