Cited by 53Neuropeptides and Animal PhysiologyGastrointestinal motility and disordersMast cells and histamine

Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats

Keita, Å. V., Carlsson, A. H., Cigéhn, M., Ericson, A.‐C., McKay, D. M., Söderholm, J. D.·2013·Neurogastroenterology & Motility

Abstract

BACKGROUND: Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. METHODS: Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess (51) chromium-edta ((51) Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP ± anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. KEY RESULTS: Stress increased (51) Cr-edta and E. coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIP-mast cell-epithelial interactions in the regulation of barrier function. CONCLUSIONS & INFERENCES: Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterial-epithelial interactions in stress-related intestinal disorders.

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Crossref · 10.1111/nmo.12127

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Authors
Keita, Å. V., Carlsson, A. H., Cigéhn, M., Ericson, A. ‐., McKay, D. M., & Söderholm, J. D.
Affiliations
  • Linköping University (SE)
  • University of Calgary (CA)
Corresponding author
Söderholm, J. D.
Venue
Neurogastroenterology & Motility
Publisher
Wiley
Published
2013-04-18
Volume
25
Issue
6
Pages
e406-17
ISSN
  • 1350-1925 (ISSN-L)
  • 1365-2982
OpenAlex
W2007043162
Cited by
53
References
52
Citations by year
2024: 4 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 2
FWCI
1.47
Type
journal article
Language
en
Open access
closed
Locations
  • Neurogastroenterology & Motility (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Keywords
vasoactive intestinal peptide, intestinal barrier function, mast cells, follicle-associated epithelium, stress, VPAC receptors, doxantrazole, mast cell stabilizers, bacterial translocation, Escherichia coli, ileum, colonic mucosa
MeSH terms
Aged, Aged, 80 and over, Animals, Female, Humans, Ileum, Intestinal Mucosa, Male, Mast Cells, Middle Aged, Permeability, Phosphodiesterase Inhibitors, Stress, Physiological, Thioxanthenes, Vasoactive Intestinal Peptide, Rats, Wistar, Receptors, Vasoactive Intestinal Peptide, Xanthones, Rats

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