Role of the intestinal barrier in inflammatory bowel disease

Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, USA.
World Journal of Gastroenterology (Impact Factor: 2.43). 02/2008; 14(3):401-7.
Source: PubMed

ABSTRACT A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells (IECs) serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex (AJC) is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease (IBD). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.

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Available from: Mike G Laukoetter, Mar 24, 2014
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    • ". illustrated in Fig. 2 [49] "
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    ABSTRACT: Necrotizing enterocolitis is a disease entity with multiple proposed pathways of pathogenesis. Various combinations of these risk factors, perhaps based on genetic predisposition, possibly lead to the mucosal and epithelial injury that is the hallmark of NEC. Intestinal epithelial integrity is controlled by a tightly regulated balance between proliferation and differentiation of epithelium from intestinal epithelial stem cells and cellular loss by apoptosis. various signaling pathways play a key role in creating and maintaining this balance. The aim of this review article is to outline intestinal epithelial barrier development and structure and the impact of these inflammatory signaling and regulatory pathways as they pertain to the pathogenesis of NEC.
    Pathophysiology 02/2014; 21(1). DOI:10.1016/j.pathophys.2014.01.001
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    • "Despite extensive research conducted over many years, the causes of IBD are still unclear. However, a defective intestinal epithelial barrier and continuous bacterial antigen stimulation of mucosal immunity have been proposed as important etiological factors of IBD in genetically susceptible individuals [5] [6] [7]. "
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    ABSTRACT: Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn's disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10(-/-)) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10(-/-) mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor- α and myeloperoxidase plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls P < 0.05). Conclusion. H. trogontum infection in IL-10(-/-) mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes.
    08/2013; 2013:909613. DOI:10.1155/2013/909613
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    • "Defects in intestinal epithelial barrier function have been proposed to play a role in a range of diseases such as the systemic inflammatory response syndrome (SIRS), sepsis, inflammatory bowel disease, asthma, allergies, type 1 diabetes, cardiovascular disease, and even autism [1] [2] [3] [4] [5]. Intestinal health-targeted therapeutic agents able to preserve intestinal barrier function have significant clinical implications in both prevention and treatment of these disease states. "
    Nutrition 05/2013; 29:1404–1411. · 3.05 Impact Factor
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