title: Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats.
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.
  
  
  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
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: A V
authors.initials: AV
authors.lastname: Keita
authors.forename: A H
authors.initials: AH
authors.lastname: Carlsson
authors.forename: M
authors.initials: M
authors.lastname: Cigéhn
authors.forename: A-C
authors.initials: AC
authors.lastname: Ericson
authors.forename: D M
authors.initials: DM
authors.lastname: McKay
authors.forename: J D
authors.initials: JD
authors.lastname: Söderholm
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010539:Permeability; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D013312:Stress, Physiological / Q000502:physiology*; D013892:Thioxanthenes / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D018005:Receptors, Vasoactive Intestinal Peptide; D013892:Thioxanthenes; D044004:Xanthones; D014660:Vasoactive Intestinal Peptide; C010134:doxantrazole