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- Söderholm, Johan D, 1958-, et al.
(author)
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Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor α
- 2004
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 53:12, s. 1817-1824
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Journal article (peer-reviewed)abstract
- Background and aims: The exact nature of the epithelial barrier defect in Crohn's disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn's disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology. Methods: Macroscopically normal segments of distal ileum of Crohn's disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor α (TNF-α) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-α on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports. Results: The area of horseradish peroxidase containing endosomes was increased (p<0.001) in enterocytes of non-inflamed ileum of Crohn's disease (2.8 (0.7) μm2/300 μm2) compared with control ileum (0.6 (0.06)). In non-inflamed mucosa, a significant association between endosomal uptake and mucosal expression of TNF-α mRNA (p = 0.03) was found. Low concentrations of TNF-α (0.25-1.0 ng/ml) enhanced the endosomal uptake of horseradish peroxidase in polarised T84 cells, without affecting transepithelial electrical resistance. Conclusions: Our findings suggest increased endosomal uptake of antigens in ileal Crohn's disease that may be mediated by TNF-α. These data highlight the transcellular route of antigen uptake in barrier dysfunction and implicate the interaction between epithelial cells and the innate immune system in the development of mucosal inflammation.
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- Zareie, M, et al.
(author)
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Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress
- 2006
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 55:11, s. 1553-1560
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Journal article (peer-reviewed)abstract
- Background and aim: Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defences against luminal bacteria. The aim of this study was to determine the ability of a defined probiotic regimen to prevent WAS induced intestinal pathophysiology. Methods: Male rats were subjected to either WAS or sham stress for one hour per day for 10 consecutive days. Additional animals received seven days of Lactobacillus helveticus and L. rhamnosus in the drinking water prior to stress and remained on these probiotics for the duration of the study. Rats were then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric lymph nodes cultured to determine bacterial translocation. Results: All animals remained healthy for the duration of the study. Chronic WAS induced excess ion secretion (elevated baseline short circuit current) and barrier dysfunction (increased conductance) in both the ileum and colon, associated with increased bacterial adhesion and penetration into surface epithelial cells. Approximately 70% of rats subjected to WAS had bacterial translocation to mesenteric lymph nodes while there was no bacterial translocation in controls. Probiotic pretreatment alone had no effect on intestinal barrier function. However, WAS induced increased ileal short circuit current was reduced with probiotics whereas there was no impact on altered conductance. Pretreatment of animals with probiotics also completely abrogated WAS induced bacterial adhesion and prevented translocation of bacteria to mesenteric lymph nodes. Conclusion: These findings indicate that probiotics can prevent chronic stress induced intestinal abnormalities and, thereby, exert beneficial effects in the intestinal tract.
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