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Journal ArticleDOI

Intestinal epithelial barrier dysfunction in Crohn's disease

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TLDR
A “leaky gut” hypothesis is advanced which proposes that a preexisting disorder of intestinal permeability is responsible for the intestinal inflammation of Crohn's disease.
Abstract
Despite extensive research, the etiology of Crohn's disease remains unknown. Accumulating evidence suggests the possibility that a primary defect of intestinal barrier function may be present in Crohn's disease. In this review, the possible role of intestinal barrier defect in Crohn's disease is discussed. It has been recognized for some time that Crohn's patients have a defective intestinal epithelial barrier function manifested by an increase in intestinal permeability. Recent studies indicate that a subgroup of healthy first-degree relatives of Crohn's patients (a population at high risk for developing Crohn's disease) also have increased intestinal permeability. Additionally, this subgroup of patients have evidence of increased exposure to foreign antigens, suggesting a possible link between increase in intestinal permeability and increase in antigenic penetration. Furthermore, exacerbation of Crohn's disease is produced by agents that disrupt intestinal epithelial barrier function, while remission of active disease is induced by decreasing intestinal antigenic load. A "leaky gut" hypothesis is advanced which proposes that a preexisting disorder of intestinal permeability is responsible for the intestinal inflammation of Crohn's disease.

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TNF-α-induced increase in intestinal epithelial tight junction permeability requires NF-κB activation

TL;DR: Crohn's disease patients have an abnormal increase in intestinal epithelial permeability, and the defect in intestinal tight junction (TJ) barrier has been proposed as an important etiologic facto barrier.
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Mechanisms regulating intestinal barrier integrity and its pathological implications.

TL;DR: A team from South Korea led by Sung Ho Ryu from Pohang University of Science and Technology review the regulatory mechanisms that help maintain the intestinal epithelial barrier and discusses the role of tight junction proteins in forming a seal between adjacent cells and the various signaling pathways that loosen or tighten these junctions to enable limited transport.
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IL-1β Causes an Increase in Intestinal Epithelial Tight Junction Permeability

TL;DR: It is shown for the first time that IL-1β at physiologically relevant concentrations causes an increase in intestinal epithelial TJ permeability.
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Mechanism of TNF-α modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression

TL;DR: Investigation of the possibility that the TNF-alpha-induced increase in intestinal epithelial TJ permeability was regulated by myosin light-chain kinase (MLCK) protein expression indicates for the first time that this mechanism was mediated by an increase in MLCK protein expression.
Journal ArticleDOI

Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2.

TL;DR: Luminal proteinases activate PAR-2 in the mouse colon to induce inflammation and disrupt the integrity of the intestinal barrier and this data may bear directly on the pathophysiology of human inflammatory bowel diseases.
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