Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment

2006 ◽  
Vol 291 (5) ◽  
pp. G938-G949 ◽  
Author(s):  
Jessica A. Clark ◽  
Sarah M. Doelle ◽  
Melissa D. Halpern ◽  
Tara A. Saunders ◽  
Hana Holubec ◽  
...  
Keyword(s):  
Cell Density ◽  
Necrotizing Enterocolitis ◽  
Goblet Cell ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Intestinal Barrier Function ◽  
Proximal Jejunum ◽  
Mucin Production ◽  
Goblet Cell Density

Necrotizing enterocolitis (NEC) is the most common intestinal disease of premature infants. Although increased mucosal permeability and altered epithelial structure have been associated with many intestinal disorders, the role of intestinal barrier function in NEC pathogenesis is currently unknown. We investigated the structural and functional changes of the intestinal barrier in a rat model of NEC. In addition, the effect of EGF treatment on intestinal barrier function was evaluated. Premature rats were divided into three groups: dam fed (DF), formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC + EGF); all groups were exposed to asphyxia/cold stress to develop NEC. Intestinal permeability, goblet cell density, mucin production, and composition of tight junction (TJ) proteins were evaluated in the terminal ileum, the site of NEC injury, and compared with the proximal jejunum, which was unaffected by NEC. Animals with NEC had significantly increased intestinal paracellular permeability compared with DF pups. Ileal goblet cell morphology, mucin production, and TJ composition were altered in animals with NEC. EGF treatment significantly decreased intestinal paracellular permeability, increased goblet cell density and mucin production, and normalized expression of two major TJ proteins, occludin and claudin-3, in the ileum. In conclusion, experimental NEC is associated with disruption of the intestinal barrier. EGF treatment maintains intestinal integrity at the site of injury by accelerating goblet cell maturation and mucin production and normalizing expression of TJ proteins, leading to improved intestinal barrier function.

scholarly journals Trifostigmanoside I, an Active Compound from Sweet Potato, Restores the Activity of MUC2 and Protects the Tight Junctions through PKCα/β to Maintain Intestinal Barrier Function

2020 ◽  
Vol 22 (1) ◽  
pp. 291
Author(s):  
Amna Parveen ◽  
Seungho Choi ◽  
Ju-Hee Kang ◽  
Seung Hyun Oh ◽  
Sun Yeou Kim
Keyword(s):  
Tight Junctions ◽  
Sweet Potato ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Human Colon ◽  
Underlying Mechanism ◽  
Intestinal Barrier Function ◽  
Isolation And Identification ◽  
Human Colon Cancer ◽  
Mucin Production

Sweet potato (Ipomoea batata) is considered a superfood among vegetables and has been consumed for centuries. Traditionally, sweet potato is used to treat several illnesses, including diarrhea and stomach disorders. This study aimed to explore the protective effect of sweet potato on intestinal barrier function, and to identify the active compounds of sweet potato and their underlying mechanism of action. To this purpose, bioactivity-guided isolation, Western blotting, and immunostaining assays were applied. Interestingly, our bioactivity-guided approach enabled the first isolation and identification of trifostigmanoside I (TS I) from sweet potato. TS I induced mucin production and promoted the phosphorylation of PKCα/β in LS174T human colon cancer cells. In addition, it protected the function of tight junctions in the Caco-2 cell line. These findings suggest that TS I rescued the impaired abilities of MUC2, and protected the tight junctions through PKCα/β, to maintain intestinal barrier function.

scholarly journals JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function

2013 ◽  
Vol 24 (18) ◽  
pp. 2849-2860 ◽  
Author(s):  
Ana C. Monteiro ◽  
Ronen Sumagin ◽  
Carl R. Rankin ◽  
Giovanna Leoni ◽  
Michael J. Mina ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Small Gtpase ◽  
Intestinal Barrier Function ◽  
Epithelial Permeability ◽  
Functional Link ◽  
Epithelial Barrier Function ◽  
And Control ◽  
Interfering Rna

Intestinal barrier function is regulated by epithelial tight junctions (TJs), structures that control paracellular permeability. Junctional adhesion molecule-A (JAM-A) is a TJ-associated protein that regulates barrier; however, mechanisms linking JAM-A to epithelial permeability are poorly understood. Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c. Supporting a functional link, small interfering RNA–mediated down-regulation of the foregoing regulatory proteins results in enhanced permeability similar to that observed after JAM-A loss. JAM-A–deficient mice and cultured epithelial cells demonstrate enhanced paracellular permeability to large molecules, revealing a potential role of JAM-A in controlling perijunctional actin cytoskeleton in addition to its previously reported role in regulating claudin proteins and small-molecule permeability. Further experiments suggest that JAM-A does not regulate actin turnover but modulates activity of RhoA and phosphorylation of nonmuscle myosin, both implicated in actomyosin contraction. These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton.

scholarly journals Bioaccessibility and Bioactivity of Cereal Polyphenols: A Review

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1595
Author(s):  
Borkwei Ed Nignpense ◽  
Nidhish Francis ◽  
Christopher Blanchard ◽  
Abishek Bommannan Santhakumar
Keyword(s):  
Barrier Function ◽  
Plasma Concentrations ◽  
Intestinal Barrier ◽  
Inflammatory Activity ◽  
Intestinal Barrier Function ◽  
Mucin Production ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
Anti Inflammatory

Cereal bioactive compounds, especially polyphenols, are known to possess a wide range of disease preventive properties that are attributed to their antioxidant and anti-inflammatory activity. However, due to their low plasma concentrations after oral intake, there is controversy regarding their therapeutic benefits in vivo. Within the gastrointestinal tract, some cereal polyphenols are absorbed in the small intestine, with the majority accumulating and metabolised by the colonic microbiota. Chemical and enzymatic processes occurring during gastrointestinal digestion modulate the bioactivity and bioaccessibility of phenolic compounds. The interactions between the cereal polyphenols and the intestinal epithelium allow the modulation of intestinal barrier function through antioxidant, anti-inflammatory activity and mucin production thereby improving intestinal health. The intestinal microbiota is believed to have a reciprocal interaction with polyphenols, wherein the microbiome produces bioactive and bioaccessible phenolic metabolites and the phenolic compound, in turn, modifies the microbiome composition favourably. Thus, the microbiome presents a key link between polyphenol consumption and the health benefits observed in metabolic conditions in numerous studies. This review will explore the therapeutic value of cereal polyphenols in conjunction with their bioaccessibility, impact on intestinal barrier function and interaction with the microbiome coupled with plasma anti-inflammatory effects.

Lactococcus lactis NZ9000 Prevents Asthmatic Airway Inflammation and Remodelling in Rats through the Improvement of Intestinal Barrier Function and Systemic TGF-β Production

2020 ◽  
pp. 1-15
Author(s):  
Daniel Cervantes-García ◽  
Mariela Jiménez ◽  
César E. Rivas-Santiago ◽  
Pamela Gallegos-Alcalá ◽  
Alicia Hernández-Mercado ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lactococcus Lactis ◽  
Lung Tissue ◽  
Goblet Cell ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Potential Candidate ◽  
Asthmatic Airway ◽  
Positive Effects

<b><i>Introduction:</i></b> The use of probiotics has been broadly popularized due to positive effects in the attenuation of aberrant immune responses such as asthma. Allergic asthma is a chronic respiratory disease characterized by airway inflammation and remodelling. <b><i>Objective:</i></b> This study was aimed to evaluate the effect of oral administration of <i>Lactococcus lactis</i> NZ9000 on asthmatic airway inflammation and lung tissue remodelling in rats and its relation to the maintenance of an adequate intestinal barrier. <b><i>Methods:</i></b> Wistar rats were ovalbumin (OVA) sensitized and challenged and orally treated with <i>L. lactis</i>. Lung inflammatory infiltrates and cytokines were measured, and remodelling was evaluated. Serum OVA-specific immunoglobulin (Ig) E levels were assessed. We also evaluated changes on intestinal environment and on systemic immune response. <b><i>Results:</i></b> <i>L. lactis</i> diminished the infiltration of proinflammatory leucocytes, mainly eosinophils, in the bronchoalveolar compartment, decreased lung IL-4 and IL-5 expression, and reduced the level of serum allergen-specific IgE. Furthermore, <i>L. lactis</i> prevented eosinophil influx, collagen deposition, and goblet cell hyperplasia in lung tissue. In the intestine, <i>L. lactis</i>-treated asthmatic rats increased Peyer’s patch and goblet cell quantity and mRNA expression of IgA, MUC-2, and claudin. Additionally, intestinal morphological alterations were normalized by <i>L. lactis</i> administration. Splenocyte proliferative response to OVA was abolished, and serum levels of transforming growth factor (TGF)-β were increased by <i>L. lactis</i> treatment. <b><i>Conclusions:</i></b> These findings suggest that <i>L. lactis</i> is a potential candidate for asthma prevention, and the effect is mediated by the improvement of intestinal barrier function and systemic TGF-β production.

scholarly journals Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

2018 ◽  
Vol 49 (1) ◽  
pp. 190-205 ◽  
Author(s):  
Yanhai Feng ◽  
Yu Wang ◽  
Pei Wang ◽  
Yalan Huang ◽  
Fengjun Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Barrier Function ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Paracellular Permeability ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Permeability Increase

Background/Aims: Short-chain fatty acids (SCFAs) are the major energy resources of intestinal epithelial cells. It has been reported that SCFAs can repair the dysfunction of intestinal barrier, however, the underlying mechanisms are still not fully understood. Here, we investigated the stimulative and protective effects of SCFAs on intestinal barrier function and the possible mechanisms. Methods: To investigate the effects of SCFAs on intestinal barrier function, the Caco-2 monolayers were exposed to acetate, propionate, butyrate respectively or simultaneously without or with lipopolysaccharide (LPS). Next, Caco-2 cells were treated with trichostatin A and etomoxir to identify whether SCFAs act as HDAC inhibitors or energy substances. To activate NLRP3 inflammasome and autophagy, Caco-2 cells were treated with LPS+ATP and rapamycin respectively without or with SCFAs. The transepithelial electrical resistance (TER) and paracellular permeability were respectively detected with a Millicell-ERS voltohmmeter and fluorescein isothiocyanate-labeled dextran. Immunoblotting and immunofluorescence were applied to analyze the expression and distribution of tight junction proteins, and the activation of NLRP3 inflammasome and autophagy. Results: Acetate (0.5mM), propionate(0.01mM) and butyrate (0.01mM) alone or in combination significantly increased TER, and stimulated the formation of tight junction. SCFAs also dramatically attenuated the LPS-induced TER reduction and paracellular permeability increase, accompanying significantly alleviated morphological disruption of ZO-1 and occludin. Meanwhile, the activation of NLRP3 inflammasome and autophagy induced by LPS were significantly inhibited by SCFAs. Trichostatin A imitated the inhibiting action of SCFAs on NLRP3 inflammasome, whereas etomoxir blocked the action of SCFAs on protecting intestinal barrier and inhibiting autophagy. In addition, the activation of autophagy and NLRP3 inflammasome by rapamycin and LPS+ATP resulted in TER reduction, paracellular permeability increase and morphological disruption of both ZO-1 and occludin, which was alleviated by SCFAs. Conclusion: It is suggested that SCFAs stimulate the formation of intestinal barrier, and protect the intestinal barrier from the disruption of LPS through inhibiting NLRP3 inflammasome and autophagy. In addition, SCFAs act as energy substances to protect intestinal barrier and inhibit autophagy, but act as HDAC inhibitors to suppress NLRP3 inflammasome. Furthermore, the mutual promoting action between NLRP3 inflammasome and autophagy would destroy intestinal barrier function, which could be alleviated by SCFAs.

W1774 Bifidobacterium Bifidum Improves Intestinal Barrier Function in Experimental Necrotizing Enterocolitis

2008 ◽  
Vol 134 (4) ◽  
pp. A-712-A-713
Author(s):  
Ludmila Khailova ◽  
Andrew Maynard ◽  
Katerina Dvorak ◽  
Kelly M. Arganbright ◽  
Melissa Halpern ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Bifidobacterium Bifidum ◽  
Intestinal Barrier Function
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