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: 2.37). 02/2008; 14(3):401-7.
Source: PubMed


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: Porfirio Nava, Sep 16, 2015
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    • "Altered permeability has been reported in those suffering from CD [24, 26, 27]. Several studies have ascertained that CD patients have an abnormal increase in intestinal permeability to paracellular markers, such as polyethylene glycol 400, cellobiose, Cr-ethylenediaminetetraacetic acid (Cr-EDTA), and lactulose [24, 26, 27]. Further studies have also shown that healthy first-degree relatives of CD patients have increased intestinal permeability with evidence of antigenic stimulation [89]. "
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    ABSTRACT: The inflammatory bowel diseases (IBD) include Crohn's disease (CD) and ulcerative colitis. The disease may present at any age although the peak of presentation is the second and third decades of life. The incidences of these diseases are increasing around the world with the age of presentation getting younger. At present CD is incurable with colectomy being the treatment for severe UC. Although several pharmacological approaches are used to modulate the inflammatory response in IBD, few lead to histological healing and most have side effects. An alternative approach is to use enteral formulae given exclusively (EEN) to treat IBD. EEN requires the consumption of an elemental or polymeric formula, with the exclusion of all other nutrients, for a period of up to 12 weeks. The introduction of EEN as a therapeutic option for IBD was through prudent observation; however, EEN has become an established and reliable option for the treatment of paediatric IBD. Despite this, the mechanisms through which EEN induces disease remission are unknown and remain hypothetical. This review will discuss recent research into EEN both describing clinical features of EEN therapy and discussing the most up-to-date understanding of the mechanisms through which EEN may be reducing intestinal inflammation and inducing disease remission.
    05/2014; 2014(5):423817. DOI:10.1155/2014/423817
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    • "Colonic epithelial cells, which act as sentinels of the mucosal immune system, are critical to the barrier and absorptive functions of the colon [9, 10]. Human colonic epithelial cells express numerous inflammatory molecules, including cytokines, chemokines, and receptors, which allow them to communicate with the immune system [11]. NF-κB is critical for the maintenance of epithelial barrier function and modulation of immune responses. "
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    ABSTRACT: To investigate the expression of adenosine A3 receptor (A3AR) in human colonic epithelial cells and the effects of A3AR activation on tumor necrosis factor alpha (TNF- α -) induced inflammation in order to determine its mechanism of action in human colonic epithelial cells, human colonic epithelial cells (HT-29 cells) were treated with different concentrations of 2-Cl-IB-MECA prior to TNF- α stimulation, followed by analysis of NF- κ B signaling pathway activation and downstream IL-8 and IL-1 β production. A3AR mRNA and protein were expressed in HT-29 cells and not altered by changes in TNF- α or 2-Cl-IB-MECA. Pretreatment with 2-Cl-IB-MECA prior to stimulation with TNF- α attenuated NF- κ B p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of I κ B- α , and reduced phosphorylated-I κ B- α level significantly, compared to TNF- α -only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF- α -stimulated IL-8 and IL-1 β mRNA expression and secretion, compared to the TNF- α -only treated group. These results confirm that A3AR is expressed in human colonic epithelial cells and demonstrate that its activation has an anti-inflammatory effect, through the inhibition of NF- κ B signaling pathway, which leads to inhibition of downstream IL-8 and IL-1 β expression. Therefore, A3AR activation may be a potential treatment for gut inflammatory diseases such as inflammatory bowel disease.
    Mediators of Inflammation 04/2014; 2014(3):818251. DOI:10.1155/2014/818251 · 3.24 Impact Factor
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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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