Importance of disrupted intestinal barrier in inflammatory bowel diseases

2011 ◽  
Vol 17 (1) ◽  
pp. 362-381 ◽  
Author(s):  
Saʼad Y. Salim ◽  
Johan D. Söderholm
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

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.

Bifidobacterium dentium N8 with potential probiotic characteristics prevents LPS-induced intestinal barrier injury by alleviating inflammatory response and regulating tight junctions in Caco-2 cell monolayers

2021 ◽  
Author(s):  
Li Zhao ◽  
Qing gang Xie ◽  
Evivie Etareri Smith ◽  
Jiahuan Dong ◽  
Deyu Liu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tight Junctions ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Protective Effects ◽  
Potential Mechanism ◽  
Cell Monolayers ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The intestinal barrier is vital in preventing inflammatory bowel diseases (IBD). This study aimed to investigate the potential mechanism behind the protective effects of B. dentium N8 on the intestinal...

Su1280 Impaired Intestinal Barrier Function Contributes to the Activation of Coagulatory Cascade in Inflammatory Bowel Diseases

2015 ◽  
Vol 148 (4) ◽  
pp. S-460
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura F. Pisani ◽  
Elena Vianello ◽  
Nadia Munizio ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Intestinal barrier dysfunction in inflammatory bowel diseases

2009 ◽  
Vol 15 (1) ◽  
pp. 100-113 ◽  
Author(s):  
Michael A. McGuckin ◽  
Rajaraman Eri ◽  
Lisa A. Simms ◽  
Timothy H.J. Florin ◽  
Graham Radford-Smith
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals IMMUNOLOGICAL AND GENETIC FEATURES OF PATHOGENETIC ASSOCIATION BETWEEN PSORIASIS AND COLONIC DYSBIOSIS.

2019 ◽  
Author(s):  
A. A. Goncharov ◽  
O. V. Dolgikh
Keyword(s):  
Bacterial Community ◽  
Single Nucleotide Polymorphisms ◽  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Bacterial Species ◽  
Intestinal Barrier ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Psoriasis is a multifactorial systemic immune-associated disease. It is assumed that colonic dysbiosis may contribute to its development. In this review we provide data on colonic dysbiosis in induction and progression of psoriatic inflammation assessing a role for bacterial species: Akkermansia muciniphila, Faecalibacterium prausnitzii and Escherichia coli. On one hand, these bacterial species indicate at state of bacterial community in dysbiosis. On the other hand, they are functionally associated with triggering a chain of events consisting in inducing impaired intestinal barrier transforming into chronic inflammation in colonic mucosa and systemic inflammation. Such scenario leads to altered systemic reactivity of innate and adaptive immune cells, impaired function of regulatory immune cells, which leads to an expansion of the autoreactive skin T-cells and induction of psoriatic inflammation due to molecular mimicry between persistent Streptococcus pyogenes and cutaneous antigens. The psoriatic process is envisioned as a comorbidity with inflammatory bowel diseases. Since dysbiotic changes in psoriasis and inflammatory bowel diseases (e. g. Crohn's disease) display similar features, these diseases might potentially proceed via a similar pathogenetic chain resulting from dysbiotic changes in intestinal microbiota to impaired intestinal barrier, chronic systemic inflammation and altered anti-inflammatory immune arm. Therefore, the data on pathogenetic pathways of diseases comorbid with psoriasis are able to uncover yet-unknown pathogenetic components for the latter. Psoriasis as a genetically-determined disease is currently believed to be associated with single nucleotide polymorphisms (SNP) in more than four hundred genes. A role for diverse SNPs in candidate genes involved in psoriasis pathogenetic chain at antigen processing and presentation, migration of immune cells, ligation and production of pro-inflammatory cytokines is discussed. Crohn's disease is associated with single nucleotide polymorphisms of genes encoding intestinal barrier proteins potentially underlying its functional deficiency. In connection with comorbidity and similarity between microbiota-associated pathogenetic psoriasis chain and inflammatory bowel diseases, it is possible to assume that such SNPs accounting for genetic defects in the intestinal barrier are manifested as dysbiotic changes in colonic bacterial community and contribute to progression not only of inflammatory bowel diseases, but psoriasis as well.

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