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Interferon-gamma re...
Interferon-gamma regulates intestinal epithelial homeostasis through converging beta-catenin signaling pathways
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- Nava, Porfirio (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Koch, Stefan (författare)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Laukoetter, Mike G. (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Department of General Surgery, Universitaet Muenster, Muenster, Germany
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- Lee, Winston Y. (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Kolegraff, Keli (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Capaldo, Christopher T. (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Beeman, Neal (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Addis, Caroline (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Gerner-Smidt, Kirsten (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Neumaier, Irmgard (författare)
- Biologische Chemie, Technische Universitaet Muenchen, Freising-Weihenstephan, Germany
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- Skerra, Arne (författare)
- Biologische Chemie, Technische Universitaet Muenchen, Freising-Weihenstephan, Germany
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- Li, Linheng (författare)
- Stowers Institute for Medical Research, Kansas City, MO, USA
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- Parkos, Charles A. (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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- Nusrat, Asma (författare)
- Epithelial Pathobiology Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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(creator_code:org_t)
- Cambridge, United States : Cell Press, 2010
- 2010
- Engelska.
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Ingår i: Immunity. - Cambridge, United States : Cell Press. - 1074-7613 .- 1097-4180. ; 32:3, s. 392-402
- Relaterad länk:
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Inflammatory cytokines have been proposed to regulate epithelial homeostasis during intestinal inflammation. We report here that interferon-gamma (IFN-gamma) regulates the crucial homeostatic functions of cell proliferation and apoptosis through serine-threonine protein kinase AKT-beta-catenin and Wingless-Int (Wnt)-beta-catenin signaling pathways. Short-term exposure of intestinal epithelial cells to IFN-gamma resulted in activation of beta-catenin through AKT, followed by induction of the secreted Wnt inhibitor Dkk1. Consequently, we observed an increase in Dkk1-mediated apoptosis upon extended IFN-gamma treatment and reduced proliferation through depletion of the Wnt coreceptor LRP6. These effects were enhanced by tumor necrosis factor-alpha (TNF-alpha), suggesting synergism between the two cytokines. Consistent with these results, colitis in vivo was associated with decreased beta-catenin-T cell factor (TCF) signaling, loss of plasma membrane-associated LRP6, and reduced epithelial cell proliferation. Proliferation was partially restored in IFN-gamma-deficient mice. Thus, we propose that IFN-gamma regulates intestinal epithelial homeostasis by sequential regulation of converging beta-catenin signaling pathways.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Animals
- Apoptosis
- Cell Line
- Cell Proliferation
- Colitis/genetics/immunology/metabolism/pathology
- Epithelial Cells/cytology/*immunology/metabolism
- *Homeostasis
- Interferon-gamma/deficiency/*immunology/metabolism
- Intestines/*immunology/metabolism
- Mice
- Mice
- Inbred C57BL
- Mice
- Knockout
- Proto-Oncogene Proteins c-akt/metabolism
- *Signal Transduction
- Wnt Proteins/metabolism
- beta Catenin/*metabolism
Publikations- och innehållstyp
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- art (ämneskategori)
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Immunity
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Nava, Porfirio
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Koch, Stefan
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Laukoetter, Mike ...
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Lee, Winston Y.
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Kolegraff, Keli
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Capaldo, Christo ...
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visa fler...
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Beeman, Neal
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Addis, Caroline
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Gerner-Smidt, Ki ...
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Neumaier, Irmgar ...
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Skerra, Arne
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Li, Linheng
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Parkos, Charles ...
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Nusrat, Asma
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