scholarly journals Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases

Proteomes ◽  
2018 ◽  
Vol 6 (2) ◽  
pp. 17 ◽  
Author(s):  
Jessica Lee ◽  
Valerie Wasinger ◽  
Yunki Yau ◽  
Emil Chuang ◽  
Vijay Yajnik ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Epithelial Barrier Dysfunction ◽  
Molecular Pathophysiology

Su2035 Functional Bowel Symptoms in Quiescent Inflammatory Bowel Diseases: Role of Epithelial Barrier Disruption and Low Grade Inflammation

2013 ◽  
Vol 144 (5) ◽  
pp. S-538 ◽  
Author(s):  
Mylène Vivinus-Nébot ◽  
Gregory Frin ◽  
Hanene Bzioueche ◽  
Raffaella Dainese ◽  
Ghislaine Bernard ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Epithelial Barrier ◽  
Low Grade ◽  
Barrier Disruption ◽  
Bowel Symptoms ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Low Grade Inflammation

Total polysaccharides of adlay bran (Coix lachryma-jobi L.) improve TNF-α induced epithelial barrier dysfunction in Caco-2 cells via inhibition of the inflammatory response

2019 ◽  
Vol 10 (5) ◽  
pp. 2906-2913 ◽  
Author(s):  
Yanlong Li ◽  
Xudong Tian ◽  
Shengcai Li ◽  
Lijun Chang ◽  
Ping Sun ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
Epithelial Barrier Dysfunction

Dysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome.

Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells

2020 ◽  
Vol 11 (4) ◽  
pp. 3741-3748 ◽  
Author(s):  
Wei Li ◽  
Mingbo Gao ◽  
Ting Han
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Inflammatory Factors ◽  
Barrier Dysfunction ◽  
Lycium Barbarum ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Lycium Barbarum Polysaccharides

Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases.

Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells

2013 ◽  
Vol 304 (11) ◽  
pp. G970-G979 ◽  
Author(s):  
Andreas Fischer ◽  
Markus Gluth ◽  
Ulrich-Frank Pape ◽  
Bertram Wiedenmann ◽  
Franz Theuring ◽  
...  
Keyword(s):  
Tight Junction ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Model Systems ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Junction Proteins

Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel diseases. Combined clinical and endoscopic remission (“mucosal healing”) in patients who received anti-TNF-α therapies suggests restitution of the intestinal barrier, but the mechanisms involved are largely unknown. We therefore investigated the impact of the anti-TNF-α antibody adalimumab on barrier function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells with interferon-γ and TNF-α resulted in a significant decrease of transepithelial electrical resistance (TEER) within 6 h that was prevented by adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore antagonized the appearance of irregular membrane undulations and prevented internalization of tight junction proteins upon cytokine exposure. In addition, TNF-α induced a downregulation of claudin-1, claudin-2, claudin-4, and occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84 but not Caco-2 cells, which was reversed by adalimumab. At the signaling level, adalimumab prevented increased phosphorylation of myosin light chain as well as activation of p38 MAPK and NF-κB accompanying the decline in TEER in both model systems. Pharmacological inhibition of NF-κB signaling partially prevented the TNF-α-induced TEER loss, whereas inhibition of p38 worsened barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data demonstrate that adalimumab prevents barrier dysfunction induced by TNF-α both functionally and structurally as well as at the level of signal transduction. Barrier protection might therefore constitute a novel mechanism how anti-TNF-α therapy contributes to epithelial restitution and tissue repair in inflammatory bowel diseases.

Mechanisms of violation of the permeability of the epithelial barrier in inflammatory bowel diseases

Pharmateca ◽  
2021 ◽  
Vol 2_2021 ◽  
pp. 30-35
Author(s):  
G.N. Tarasova Tarasova ◽  
A.A. Iakovlev Iakovlev ◽  
A.D. Zubova Zubova ◽  
S.M. Nukhova Nukhova ◽  
◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation

Gut ◽  
2013 ◽  
Vol 63 (5) ◽  
pp. 744-752 ◽  
Author(s):  
M Vivinus-Nébot ◽  
G Frin-Mathy ◽  
H Bzioueche ◽  
R Dainese ◽  
G Bernard ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Epithelial Barrier ◽  
Low Grade ◽  
Barrier Disruption ◽  
Bowel Symptoms ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Low Grade Inflammation

scholarly journals DOP51 Investigation on the role of Par4-associated cell polarity and associated barrier defects in inflammatory bowel diseases

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S089-S089
Author(s):  
F Branchi ◽  
C Heldt ◽  
B Siegmund ◽  
M Schumann
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Inflammatory Bowel Diseases ◽  
Laser Scanning Microscopy ◽  
Immunofluorescent Staining ◽  
Epithelial Barrier ◽  
Western Blots ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background In inflammatory bowel diseases (IBD), epithelial barrier defects occur as a consequence of chronic inflammation. Recent research suggested that cell polarity alterations may be upstream of barrier defects and additionally play a role in IBD-associated carcinogenesis (colitis-associated and small intestinal carcinoma). Par4 is a gene encoding a protein crucial in the development of cell polarity. LKB1, its human homologue, is mutated in Peutz–Jeghers syndrome (PJS), a genetic condition characterised by a higher risk of epithelial cancers. While the pivotal role of Par4/LKB1 in the development of epithelial cell polarity is established, its involvement in IBD-associated barrier defects and carcinogenesis is yet to be defined. Methods Endoscopic bowel mucosa samples from patients with Crohn’s disease, ulcerative colitis, PJS and controls were analysed to assess expression and localisation of Par4/LKB1. Cryosections were immunostained for Par4/LKB-1 along with a diverse set of markers of cell polarity and intercellular adhesion. The analysis was performed by confocal laser scanning microscopy in order to compare the expression of mucosal as well as the subcellular localisation of Par4/LKB1 in the gut mucosa. A quantitative analysis of protein expression with western blotting was performed as well. The function of Par4/LKB1 in intestinal epithelial cells (IEC) was evaluated by means of a Par4-deficient IEC model as well as in an IEC Par4-overexpression model. Moreover, a preliminary assessment of the possible role of Par4/LKB1-related polarity processes in IBD-associated carcinomas was performed through scanning genetic data from colitis-associated carcinomas for potential Par4-related mutations and altered Par4/LKB1 expression. Results The immunofluorescent staining allowed visualisation of intracellular expression of Par4 in epithelia from PJS, IBD patients and controls. In PJS-polyps, despite the alteration of regular tissue architecture typical of these lesions, the polarity of epithelial cells was maintained - contrary to control tissue, a punctate pattern of the Par4 staining was shown. In IBD tissue, no relevant differences in Par4 expression at confocal microscopy, as well as a quantitative assessment, were observed as compared with controls. No differences were observed in PJS or IBD samples as regards the expression of cell polarity markers such as Par3, CD71, crb3 or adhesion molecules such as ZO-1, e-cadherin, occludin, JAM-A. As regards the IEC model, we observed that Caco-2/BBe cells overexpressing Par4/LKB1 showed enhanced Par4/LKB1 cytosolic staining at immunofluorescence. In this model, a defective epithelial polarity and organisation on permeable supports could be observed in Caco2/BBe cysts in parallel with reduced expression of native LKB1 as seen in western blots. Preliminary analysis of data from our colitis-associated carcinomas database suggested various pathways potentially involving Par4/LKB1, yet no direct analysis of tissue samples for Par4-related mutations was performed yet. Conclusions Altered expression of Par4 in epithelial cells may influence the development of a functional epithelial barrier as suggested by IEC models. Par4/LKB1 as a known oncosuppressor gene is involved in a number of pathways potentially relevant for carcinogenesis in IBD; however, a direct connection between Par4-related alteration of the epithelial barrier and carcinogenesis is yet to be established.

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