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Erschienen in:
01.02.2012 | Original Article—Alimentary Tract
Differential effects of nutritional and non-nutritional therapies on intestinal barrier function in an in vitro model
Erschienen in: Journal of Gastroenterology | Ausgabe 2/2012
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Background
Diminished intestinal epithelial barrier function contributes to the pathogenesis of Crohn’s disease. Clinical and experimental studies propose that increased tumor necrosis factor (TNF)-α promotes barrier dysfunction. The aim of this study was to investigate the effects of nutritional and other therapies upon intestinal barrier function in the presence of TNF-α in an in vitro model.
Methods
Caco-2 monolayers were grown to confluence on membrane supports and then exposed to TNF-α in the presence of polymeric formula, hydrocortisone or infliximab. Monolayer permeability was evaluated by measuring epithelial resistance, short-circuit current and horseradish peroxidase flux in an Ussing chamber. Tight junction and myosin II regulatory light-chain kinase gene expression was analysed by real-time PCR, with protein expression and localization analysed by Western blot and immunofluorescence.
Results
TNF-α increased monolayer permeability and diminished tight junction integrity. However both polymeric formula and infliximab completely abrogated the effects of TNF-α. These monolayers displayed unchanged permeability and tight junction integrity compared to untreated cells (media-no-TNF-α controls). In contrast, hydrocortisone only partially abrogated the effects of TNF-α, with these monolayers having increased permeability and altered tight junction integrity compared to media-no-TNF-α controls.
Conclusions
Both polymeric formula and infliximab completely prevent epithelial barrier dysfunction in the presence of TNF-α, whereas hydrocortisone partially prevents barrier dysfunction. These results provide evidence that superior mucosal healing can be achieved with both polymeric formula and infliximab compared to hydrocortisone.