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Mucosal Immunol. 2014 Mar;7(2):369-78. doi: 10.1038/mi.2013.55. Epub 2013 Jul 31.

TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells.

Author information

1
Department of Gastroenterology, Division of Nutritional Medicine, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
2
1] Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany [2] Institute of Anatomy II, University of Jena, Jena, Germany.
3
Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Munich, Germany.
5
Institute of Immunology, Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
6
1] Department of Gastroenterology, Division of Nutritional Medicine, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany [2] Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
7
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

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.

PMID:
23900194
DOI:
10.1038/mi.2013.55
[Indexed for MEDLINE]

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