Back to Search
Start Over
Pathogenic Bacteria Induce Colonic PepT1 Expression: An Implication in Host Defense Response
- Source :
- Gastroenterology. 137:1435-1447.e2
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Background & Aims Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions; however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Methods Human colonic HT29-Cl.19A cells were infected with the attaching and effacing enteropathogenic Escherichia coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium , a murine attaching and effacing pathogen related to EPEC. Results EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of nuclear factor-κB and mitogen-activated protein kinase and production of interleukin-8. Accordingly, ex vivo and in vivo experiments revealed that C rodentium induced colonic PepT1 expression and that, compared with their wild-type counterparts, PepT1 transgenic mice infected with C rodentium exhibited decreased bacterial colonization, production of proinflammatory cytokines, and neutrophil infiltration into the colon. Conclusions Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathologic conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation.
- Subjects :
- Genetically modified mouse
Time Factors
Transcription, Genetic
Colon
Mice, Transgenic
Biology
Transfection
medicine.disease_cause
Peptide Transporter 1
digestive system
Bacterial Adhesion
Article
Proinflammatory cytokine
Microbiology
Enteropathogenic Escherichia coli
Mice
Membrane Microdomains
medicine
Citrobacter rodentium
Animals
Humans
CDX2 Transcription Factor
RNA, Messenger
Intestinal Mucosa
Promoter Regions, Genetic
Protein kinase A
Lipid raft
Homeodomain Proteins
Symporters
Hepatology
Interleukin-8
NF-kappa B
Gastroenterology
Pathogenic bacteria
Colitis
digestive system diseases
Disease Models, Animal
Neutrophil Infiltration
Inflammation Mediators
Mitogen-Activated Protein Kinases
HT29 Cells
Ex vivo
Subjects
Details
- ISSN :
- 00165085
- Volume :
- 137
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi.dedup.....29c04879a521f5beb21f7eebc82e645e