scholarly journals Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

2020 ◽  
Vol 231 (1) ◽  
Author(s):  
Nicolas Schlegel ◽  
Kevin Boerner ◽  
Jens Waschke
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Experimental Models ◽  
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.

scholarly journals The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand?

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3402
Author(s):  
Barbara Borsani ◽  
Raffaella De Santis ◽  
Veronica Perico ◽  
Francesca Penagini ◽  
Erica Pendezza ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Experimental Models ◽  
Gelling Agent ◽  
Current Evidence ◽  
Allergic Reactions ◽  
Processed Foods ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Carrageenan (CGN) is a high molecular weight polysaccharide extracted from red seaweeds, composed of D-galactose residues linked in β-1,4 and α-1,3 galactose-galactose bond, widely used as a food additive in processed foods for its properties as a thickener, gelling agent, emulsifier, and stabilizer. In recent years, with the spread of the Western diet (WD), its consumption has increased. Nonetheless, there is a debate on its safety. CGN is extensively used as an inflammatory and adjuvant agent in vitro and in animal experimental models for the investigation of immune processes or to assess the activity of anti-inflammatory drugs. CGN can activate the innate immune pathways of inflammation, alter the gut microbiota composition and the thickness of the mucus barrier. Clinical evidence suggests that CGN is involved in the pathogenesis and clinical management of inflammatory bowel diseases (IBD), indeed food-exclusion diets can be an effective therapy for disease remission. Moreover, specific IgE to the oligosaccharide α-Gal has been associated with allergic reactions commonly referred to as the “α-Gal syndrome”. This review aims to discuss the role of carrageenan in inflammatory bowel diseases and allergic reactions following the current evidence. Furthermore, as no definitive data are available on the safety and the effects of CGN, we suggest gaps to be filled and advise to limit the human exposure to CGN by reducing the consumption of ultra-processed foods.

scholarly journals A review of the efficacy of dietary polyphenols in experimental models of inflammatory bowel diseases

2015 ◽  
Vol 6 (6) ◽  
pp. 1773-1786 ◽  
Author(s):  
Derek A. Martin ◽  
Bradley W. Bolling
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Experimental Models ◽  
Rodent Models ◽  
Dietary Polyphenols ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Higher Doses

The use of polyphenols in rodent models of inflammatory bowel diseases is reviewed. Many polyphenols inhibit colitis through multiple mechanisms, however higher doses of some treatments may exacerbate inflammation.

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...

scholarly journals Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

2011 ◽  
Vol 300 (2) ◽  
pp. G191-G201 ◽  
Author(s):  
Fayez K. Ghishan ◽  
Pawel R. Kiela
Keyword(s):  
Vitamin D ◽  
Bone Metabolism ◽  
Inflammatory Mediators ◽  
Inflammatory Bowel Diseases ◽  
Experimental Models ◽  
Mineral Density ◽  
Anabolic Hormone ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammation-associated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD.

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