Abstract |
The probiotic Escherichia coli Nissle 1917 ( EcN) is widely used to maintain remission in ulcerative colitis. This is thought to be mediated by various immunomodulatory and barrier-stabilizing effects in the intestine. In this study, the mechanisms of barrier modulation by EcN were studied in the human epithelial HT-29/B6 cell culture model. EcN supernatant increased transepithelial resistance (TER) and reduced permeability to mannitol because of sealing of the paracellular passage pathway as revealed by two-path impedance spectroscopy. This increase in TER was attributed to the TcpC protein of EcN. TcpC induced protein kinase C-ζ (PKCζ) and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which in turn resulted in upregulation of the barrier-forming tight junction protein claudin-14. By specific silencing of protein expression by small interfering RNA ( siRNA), the sealing function of claudin-14 was confirmed. In conclusion, the TcpC protein of EcN affects innate immunity by improving intestinal barrier function through upregulation of claudin-14 via PKCζ and ERK1/2 signaling.
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Authors | N A Hering, J F Richter, A Fromm, A Wieser, S Hartmann, D Günzel, R Bücker, M Fromm, J D Schulzke, H Troeger |
Journal | Mucosal immunology
(Mucosal Immunol)
Vol. 7
Issue 2
Pg. 369-78
(Mar 2014)
ISSN: 1935-3456 [Electronic] United States |
PMID | 23900194
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Claudins
- Escherichia coli Proteins
- TcpC protein, E coli
- Virulence Factors
- Protein Kinase C
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- claudin 14
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Topics |
- Animals
- Animals, Newborn
- Cell Line
- Claudins
(metabolism)
- Epithelial Cells
(drug effects, metabolism)
- Escherichia coli
(metabolism)
- Escherichia coli Proteins
(genetics, metabolism, pharmacology)
- Gene Knockout Techniques
- HT29 Cells
- Humans
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Mucous Membrane
(drug effects, immunology, metabolism)
- Permeability
- Phosphorylation
(drug effects)
- Protein Kinase C
(metabolism)
- Signal Transduction
(drug effects)
- Swine
- Virulence Factors
(genetics, metabolism, pharmacology)
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