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Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction
Open accessAbstract
BACKGROUND AND AIMS: Stressful life events are known to modulate the development or relapse of disease in both inflammatory bowel disease and irritable bowel disease patients but underlying mechanisms remain unclear. Stress is known to effect mast cells, interferon gamma (IFN-gamma), and myosin light chain phosphorylation to trigger colonic epithelial barrier dysfunction. The aim of this study was to investigate whether acute stress induced or chemical mast cell activation impaired expression and function of epithelial tight junctions, and altered colonocyte differentiation in mice. METHODS: Colonic paracellular permeability was assessed as the in vivo lumen to blood ratio of 51Cr-EDTA in different groups of mice (controls, stressed, mast cell degranulator BrX-537A treated), pretreated or not with the mast cell stabiliser doxantrazole. Involvement of mast cells and IFN-gamma was evaluated in wild-type and IFN-gamma deficient mice. Tight junction alteration was assessed by histology, transmission electron microscopy, and real time reverse transcription-polymerase chain reaction. Colonocyte differentiation was determined by protein kinase C zeta (PKCzeta) immunofluorescence and western blotting, and alkaline phosphatase activity assay. RESULTS: Acute stress induced a three day delayed increase in colonic paracellular permeability which involved mast cell degranulation and overproduction of IFN-gamma. The colonic epithelial barrier was morphologically altered and expression of mRNA encoding tight junction proteins ZO-2 and occludin was decreased. Moreover, three days after acute stress, colonocyte differentiation was reduced, as shown by decreased expression of both PKCzeta isotype and alkaline phosphatase. CONCLUSION: These data highlight new mechanisms whereby an acute stress acts on the gastrointestinal tract by inducing alterations in colonocyte differentiation and decreased expression of mRNA encoding tight junction proteins. Thus phenotypic changes in colonocytes could pave the way for stress related intestinal disorders.
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“Mechanistically, inflammatory intestinal leukocytes, including IL17+ T cells as well as mast cells, may contribute to the breakdown of the intestinal epithelial barrier and the accompanying downregulation of tight junction proteins CLDN5, occludin (OCLN) and tight junction protein 2 (ZO-2)106,107.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [107]
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“Stress-induced changes in permeability involve activation of glial and mast cells in the gut, overproduction of interferon-γ and changes in the morphology of the colonic epithelium via reduced expression of tight junction protein 2 (zona occludens 2) and by occlusion of important components of the intestinal tight junction.28”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [28]
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Metadata
- Authors
- Demaude, J.
- Affiliations
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Corresponding author
- Demaude, J
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2006-05-01
- Volume
- 55
- Issue
- 5
- Pages
- 655-661
- ISSN
- 0017-5749 (ISSN-L)
- PMC
- PMC1856132
- OpenAlex
- W2119510464
- Cited by
- 167
- References
- 47
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 12
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Institut National de la Recherche Agronomique
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- acute stress, mast cell activation, mast cell degranulation, tight junction proteins, ZO-2, occludin, interferon-gamma, doxantrazole, paracellular permeability, protein kinase C zeta, alkaline phosphatase, irritable bowel disease, inflammatory bowel disease
- MeSH terms
- Alkaline Phosphatase, Animals, Cell Differentiation, Cell Membrane Permeability, Colon, Epithelial Cells, Interferon-gamma, Intestinal Mucosa, Male, Mast Cells, Membrane Proteins, Mice, Inbred Strains, Phosphorylation, Protein Kinase C, Stress, Psychological, Time Factors, Cell Degranulation, Mice, Knockout, Myosin Light Chains, Tight Junctions, Reverse Transcriptase Polymerase Chain Reaction, Microscopy, Electron, Transmission, Mice, Occludin, Zonula Occludens-2 Protein
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