title: TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells.
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.
authors.affiliation: Department of Gastroenterology, Division of Nutritional Medicine, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: N A
authors.initials: NA
authors.lastname: Hering
authors.affiliation: 1] Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany [2] Institute of Anatomy II, University of Jena, Jena, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Richter
authors.affiliation: Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fromm
authors.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wieser
authors.affiliation: Institute of Immunology, Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Günzel
authors.affiliation: Department of Gastroenterology, Division of Nutritional Medicine, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bücker
authors.affiliation: Institute of Clinical Physiology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fromm
authors.affiliation: 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.
authors.forename: J D
authors.initials: JD
authors.lastname: Schulzke
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Troeger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D057167:Claudins / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D055786:Gene Knockout Techniques; D019073:HT29 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010539:Permeability; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D057167:Claudins; D029968:Escherichia coli Proteins; C549538:TcpC protein, E coli; D037521:Virulence Factors; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C422064:claudin 14
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