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Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease

Soderholm, JD; Olaison, G; Peterson, KH; Franzén, Lina LU ; Lindmark, T; Wiren, M; Tagesson, C and Sjodahl, R (2002) In Gut 50(3). p.307-313
Abstract
Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Methods: Mucosal permeability to C-51-EDTA and electrical resistance were... (More)
Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Methods: Mucosal permeability to C-51-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability-that is, increased permeation of Cr-51-EDTA and decreased electrical resistance-which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Gut
volume
50
issue
3
pages
307 - 313
publisher
BMJ Publishing Group
external identifiers
  • wos:000174003600007
  • scopus:0036177947
ISSN
1468-3288
DOI
10.1136/gut.50.3.307
language
English
LU publication?
yes
id
27f18489-2cdb-4f25-b46b-daa16ce84c86 (old id 343191)
alternative location
http://gut.bmj.com/cgi/content/abstract/50/3/307
date added to LUP
2007-11-14 12:57:24
date last changed
2017-12-10 04:38:57
@article{27f18489-2cdb-4f25-b46b-daa16ce84c86,
  abstract     = {Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Methods: Mucosal permeability to C-51-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability-that is, increased permeation of Cr-51-EDTA and decreased electrical resistance-which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.},
  author       = {Soderholm, JD and Olaison, G and Peterson, KH and Franzén, Lina and Lindmark, T and Wiren, M and Tagesson, C and Sjodahl, R},
  issn         = {1468-3288},
  language     = {eng},
  number       = {3},
  pages        = {307--313},
  publisher    = {BMJ Publishing Group},
  series       = {Gut},
  title        = {Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease},
  url          = {http://dx.doi.org/10.1136/gut.50.3.307},
  volume       = {50},
  year         = {2002},
}