scholarly journals Caprate Modulates Intestinal Barrier Function in Porcine Peyer’s Patch Follicle-Associated Epithelium

2019 ◽  
Vol 20 (6) ◽  
pp. 1418 ◽  
Author(s):  
Judith Radloff ◽  
Valeria Cornelius ◽  
Alexander G. Markov ◽  
Salah Amasheh
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Barrier Properties ◽  
Food Allergies ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Food Component ◽  
Follicle Associated Epithelium

Background: Many food components influence intestinal epithelial barrier properties and might therefore also affect susceptibility to the development of food allergies. Such allergies are triggered by increased antibody production initiated in Peyer’s patches (PP). Usually, the presentation of antigens in the lumen of the gut to the immune cells of the PP is strongly regulated by the follicle-associated epithelium (FAE) that covers the PP. As the food component caprate has been shown to impede barrier properties in villous epithelium, we hypothesized that caprate also affects the barrier function of the PP FAE, thereby possibly contributing a risk factor for the development of food allergies. Methods: In this study, we have focused on the effects of caprate on the barrier function of PP, employing in vitro and ex vivo experimental setups to investigate functional and molecular barrier properties. Incubation with caprate induced an increase of transepithelial resistance, and a marked increase of permeability for the paracellular marker fluorescein in porcine PP to 180% of control values. These effects are in accordance with changes in the expression levels of the barrier-forming tight junction proteins tricellulin and claudin-5. Conclusions: This barrier-affecting mechanism could be involved in the initial steps of a food allergy, since it might trigger unregulated contact of the gut lumen with antigens.

scholarly journals Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Dianne Pupo Gómez ◽  
Francois Boudreau
Keyword(s):  
Intestinal Epithelium ◽  
Cell Lineage ◽  
Intestinal Barrier ◽  
Barrier Properties ◽  
Cell Types ◽  
Food Allergies ◽  
Complex Nature ◽  
Intestinal Epithelial ◽  
Normal Epithelium

Maintenance of intestinal epithelium homeostasis is a complex process because of the multicellular and molecular composition of the gastrointestinal wall and the involvement of surrounding interactive signals. The complex nature of this intestinal barrier system poses challenges in the detailed mechanistic understanding of intestinal morphogenesis and the onset of several gut pathologies, including intestinal inflammatory disorders, food allergies, and cancer. For several years, the gut scientific community has explored different alternatives in research involving animals and in vitro models consisting of cultured monolayers derived from the immortalized or cancerous origin cell lines. The recent ability to recapitulate intestinal epithelial dynamics from mini-gut cultures has proven to be a promising step in the field of scientific research and biomedicine. The organoids can be grown as two- or three-dimensional structures, and are derived from adult or pluripotent stem cells that ultimately establish an intestinal epithelium that is composed of all differentiated cell types present in the normal epithelium. In this review, we summarize the different origins and recent use of organoids in modeling intestinal epithelial differentiation and barrier properties.

Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route

2017 ◽  
Vol 313 (6) ◽  
pp. G537-G548 ◽  
Author(s):  
Silke S. Zakrzewski ◽  
Michael Fromm ◽  
Jörg D. Schulzke ◽  
Dorothee Günzel
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Secretory Diarrhea ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Gastrointestinal Infections ◽  
Apical Side

During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. To analyze the molecular mechanism whereby Zn acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools. Feeding pharmacological Zn doses exerted no significant electrophysiologically ascertainable short- and long-term effects on jejunal barrier function ex vivo. However, in IPEC-J2/PS, basolateral Zn was cytotoxic since its application caused a release of lactate dehydrogenase and an irreversible breakdown of the epithelial barrier. In contrast, apical Zn application caused an immediate increase in paracellular resistance and a decrease in permeability to the paracellular marker fluorescein, reflecting overall barrier strengthening in vitro. Apical effects were fully reversible upon washout. This indicates that Zn supplemented to feed was completely washed out during ex vivo jejunum preparation. We conclude that there is no evidence for long-term barrier effects through prophylactic Zn supplementation and that extracellular Zn acts acutely and reversibly from the apical side via tightening the paracellular route, thus counteracting leak-flux diarrhea. NEW & NOTEWORTHY Therapeutically administered Zn successfully treats diarrhea in veterinary and human medicine. Here we present data that Zn strengthens the porcine jejunal epithelial barrier by reversibly tightening the paracellular route for inorganic ions and small solutes. Acute or long-lasting Zn effects on transcellular transport (Cl− secretion) were not detected. We therefore conclude that Zn is useful for acutely treating leak-flux diarrhea rather than secretory diarrhea. Suitability as prophylactic feed supplement, however, is questionable.

MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig

2017 ◽  
Vol 312 (5) ◽  
pp. G434-G442 ◽  
Author(s):  
Yuhua Zhu ◽  
Wei Wang ◽  
Taolin Yuan ◽  
Liangliang Fu ◽  
Lian Zhou ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Regulation Mechanism ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Intrauterine Growth

An important characteristic of intrauterine growth restricted (IUGR) neonate is the impaired intestinal barrier function. With the use of a pig model, this study was conducted to identify the responsible microRNA (miRNA) for the intestinal damage in IUGR neonates through comparing the miRNA profile of IUGR and normal porcine neonates and to investigate the regulation mechanism. Compared with the normal ones, we identified 83 upregulated and 76 downregulated miRNAs in the jejunum of IUGR pigs. Notably, IUGR is associated with profoundly increasesd miR-29 family and decreased expression of extracellular matrix (ECM) and tight junction (TJ) proteins in the jejunum. Furthermore, in vitro study using theporcine intestinal epithelial cell line (IPEC-1) showed that inhibition of miR-29a expression could improve the monolayer integrity by increasing cell proliferation and transepithelial resistance. Also, overexpression/inhibition of miR-29a in IPEC-1 cells can suppress/increase the expression of integrin-β1, collagen I, collagen IV, fibronectin, and claudin 1, both at transcriptional and translational levels. Subsequent luciferase reporter assay confirmed a direct interaction between miR-29a and the 3′-untranslated regions of these genes. In conclusion, this study reveals that IUGR-impaired intestinal barrier function is associated with downregulated ECM and TJ protein expression mediated by the upregulation of miR-29a. NEW & NOTEWORTHY Intrauterine growth restricted (IUGR) remains a major problem for both human health and animal production due to its association with high rates of preweaning morbidity and mortality. We have identified the abnormal expression of microRNA-29a (miR-29a) in the small intestine of IUGR neonates, as well as its targets and mechanisms. These results provide new information about biological characteristics of IUGR-affected intestinal dysfunction and can lead to the development of potentially solution for preventing and treating IUGR in the future.

scholarly journals 124 Butyric acid and derivatives: In vitro effects on barrier integrity of porcine intestinal epithelial cells quantified by transepithelial electrical resistance

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 109-110
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Butyric Acid ◽  
Sodium Butyrate ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

Abstract Intestinal barrier function in vitro is quantified by the transepithelial electrical resistance (TEER) across epithelial cell monolayers due to polarization and expression of tight junction proteins. The objective of the current study was to measure the TEER of porcine intestinal epithelial cells (IPEC-J2) treated with butyric acid, sodium butyrate, monobutyrin and tributyrin. MTT assays were performed for each compound to determine cell viability and appropriate treatment doses. Butyric acid and tributyrin treatments were: 0, 0.5, 1, 2, and 4 mM. Monobutyrin and sodium butyrate doses were: 0, 1, 2, 4, 8 mM. Cells were seeded at 5 × 105 cells/mL into 12-well plates on Corning transwell inserts. Cells were cultured for 4 to 5 days (until all wells had TEER close to 1000 Ωcm2) and were then treated with organic acids. Each compound was tested in a randomized complete block design with 10 replicates. TEER was measured in Ωcm2 using a Millicell ERS-2 voltohmmeter at 0 h (before treatment) and at 24, 48, and 72 h post-treatment. All data were analyzed by PROC MIXED of SAS. Butyric acid linearly enhanced (P < 0.001) TEER of IPEC-J2 dose-dependently, with the highest TEER observed at doses of 1 and 2 mM at each time point. Sodium butyrate did not impact TEER at h 24, but linearly increased (P < 0.05) TEER at h 48 and 72. Treatment of monobutyrin linearly improved (P < 0.001) TEER at h 24, 48, and 72, with the highest TEER observed at the dose of 8 mM. Tributyrin had the tendency to improve (P < 0.10) TEER at h 48 and 72 when the highest dose was applied. Results of the current in vitro study indicate that butyric acid and its derivatives may improve intestinal barrier function of pigs, which requires verification in vivo.

scholarly journals Plectin ensures intestinal epithelial integrity and protects colon against colitis

2021 ◽  
Vol 14 (3) ◽  
pp. 691-702
Author(s):  
Alzbeta Krausova ◽  
Petra Buresova ◽  
Lenka Sarnova ◽  
Gizem Oyman-Eyrilmez ◽  
Jozef Skarda ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Intestinal Barrier ◽  
Intercellular Junctions ◽  
Protein Profiling ◽  
Cell Junctions ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Critical Determinant ◽  
In Vitro Feeding

AbstractPlectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

scholarly journals Arctigenin fromFructus Arctii(Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hee Soon Shin ◽  
Sun Young Jung ◽  
Su Yeon Back ◽  
Jeong-Ryong Do ◽  
Dong-Hwa Shon
Keyword(s):  
Barrier Function ◽  
Active Component ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Traditional Herbal Medicine ◽  
Cell Monolayers ◽  
Basolateral Side

Fructus Arctiiis used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect ofF. Arctiiextract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component ofF. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment ofF. Arctiiincreased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component ofF. Arctiiincreased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed thatF. Arctiicould enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin fromF. Arctiicould contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

scholarly journals Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Barrier Function ◽  
Structural Integrity ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.

The Effects of Sulfated Secondary Bile Acids on Intestinal Barrier Function and Immune Response in an Inflammatory in vitro Human Intestinal Model

2021 ◽  
Author(s):  
Benthe van der Lugt ◽  
Maartje C.P. Vos ◽  
Mechteld Grootte Bromhaar ◽  
Noortje Ijssennagger ◽  
Frank Vrieling ◽  
...  
Keyword(s):  
Immune Response ◽  
Bile Acids ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Secondary Bile Acids

scholarly journals The mRNA-binding protein IGF2BP1 maintains intestinal barrier function by up-regulating occludin expression

2020 ◽  
Vol 295 (25) ◽  
pp. 8602-8612
Author(s):  
Vikash Singh ◽  
Chethana P. Gowda ◽  
Vishal Singh ◽  
Ashwinkumar S. Ganapathy ◽  
Dipti M. Karamchandani ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Barrier Function ◽  
Binding Protein ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Adult Mice ◽  
Junction Protein ◽  
Mrna Binding Protein ◽  
Mrna Binding

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an mRNA-binding protein that has an oncofetal pattern of expression. It is also expressed in intestinal tissue, suggesting that it has a possible role in intestinal homeostasis. To investigate this possibility, here we generated Villin CreERT2:Igf2bp1flox/flox mice, which enabled induction of an IGF2BP1 knockout specifically in intestinal epithelial cells (IECs) of adult mice. Using gut barrier and epithelial permeability assays and several biochemical approaches, we found that IGF2BP1 ablation in the adult intestinal epithelium causes mild active colitis and mild-to-moderate active enteritis. Moreover, the IGF2BP1 deletion aggravated dextran sodium sulfate–induced colitis. We also found that IGF2BP1 removal compromises barrier function of the intestinal epithelium, resulting from altered protein expression at tight junctions. Mechanistically, IGF2BP1 interacted with the mRNA of the tight-junction protein occludin (Ocln), stabilizing Ocln mRNA and inducing expression of occludin in IECs. Furthermore, ectopic occludin expression in IGF2BP1-knockdown cells restored barrier function. We conclude that IGF2BP1-dependent regulation of occludin expression is an important mechanism in intestinal barrier function maintenance and in the prevention of colitis.

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