scholarly journals Allomyrina dichotoma larval extract attenuates intestinal barrier disruption by altering inflammatory response and tight junction proteins in lipopolysaccharide-induced Caco-2 cells

2020 ◽  
Vol 532 (1) ◽  
pp. 145-150
Author(s):  
Kyong Kim ◽  
Gong-Deuk Bae ◽  
Eun-Young Park ◽  
Dong Jae Baek ◽  
Chul Young Kim ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tight Junction ◽  
Intestinal Barrier ◽  
Tight Junction Proteins ◽  
Barrier Disruption ◽  
Junction Proteins

scholarly journals Antibiotic-Induced Gut Microbiota Dysbiosis Damages the Intestinal Barrier, Increasing Food Allergy in Adult Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3315
Author(s):  
Qiuyu Zhang ◽  
Lei Cheng ◽  
Junjuan Wang ◽  
Mengzhen Hao ◽  
Huilian Che
Keyword(s):  
Food Allergy ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Tight Junction ◽  
Intestinal Barrier ◽  
Later Life ◽  
Food Allergies ◽  
Tight Junction Proteins ◽  
Gut Microbiota Dysbiosis ◽  
Junction Proteins

(1) Background: The use of antibiotics affects the composition of gut microbiota. Studies have suggested that the colonization of gut microbiota in early life is related to later food allergies. Still, the relationship between altered intestinal microbiota in adulthood and food allergies is unclear. (2) Methods: We established three mouse models to analyze gut microbiota dysbiosis’ impact on the intestinal barrier and determine whether this effect can increase the susceptibility to and severity of food allergy in later life. (3) Results: The antibiotic-induced gut microbiota dysbiosis significantly reduced Lachnospiraceae, Muribaculaceae, and Ruminococcaceae, and increased Enterococcaceae and Clostridiales. At the same time, the metabolic abundance was changed, including decreased short-chain fatty acids and tryptophan, as well as enhanced purine. This change is related to food allergies. After gut microbiota dysbiosis, we sensitized the mice. The content of specific IgE and IgG1 in mice serum was significantly increased, and the inflammatory response was enhanced. The dysbiosis of gut microbiota caused the sensitized mice to have more severe allergic symptoms, ruptured intestinal villi, and a decrease in tight junction proteins (TJs) when re-exposed to the allergen. (4) Conclusions: Antibiotic-induced gut microbiota dysbiosis increases the susceptibility and severity of food allergies. This event may be due to the increased intestinal permeability caused by decreased intestinal tight junction proteins and the increased inflammatory response.

scholarly journals The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction

2010 ◽  
Vol 298 (5) ◽  
pp. G625-G633 ◽  
Author(s):  
Wei Zhong ◽  
Craig J. McClain ◽  
Matthew Cave ◽  
Y. James Kang ◽  
Zhanxiang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Zinc Deficiency ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Alcohol Exposure ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Junction Proteins

Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.

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.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Leah Hernandez ◽  
Liam Ward ◽  
Thomas Ebert ◽  
Samsul Arefin ◽  
Olof Heimbürger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tight Junction ◽  
Kidney Transplant ◽  
Subcutaneous Fat ◽  
Intestinal Barrier ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

scholarly journals Tricellular Tight Junction Protein Tricellulin Is Targeted by the Enteropathogenic Escherichia coli Effector EspG1, Leading to Epithelial Barrier Disruption

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Vijay Morampudi ◽  
Franziska A. Graef ◽  
Martin Stahl ◽  
Udit Dalwadi ◽  
Victoria S. Conlin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tight Junction ◽  
Significant Loss ◽  
Effector Proteins ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Barrier Disruption ◽  
Junction Protein ◽  
Junction Proteins

ABSTRACT Enteropathogenic Escherichia coli (EPEC)-induced diarrhea is often associated with disruption of intestinal epithelial tight junctions. Although studies have shown alterations in the expression and localization of bicellular tight junction proteins during EPEC infections, little is known about whether tricellular tight junction proteins (tTJs) are affected. Using Caco-2 cell monolayers, we investigated if EPEC is capable of targeting the tTJ protein tricellulin. Our results demonstrated that at 4 h postinfection, EPEC induced a significant reduction in tricellulin levels, accompanied by a significant loss of transepithelial resistance (TEER) and a corresponding increase in paracellular permeability. Conversely, cells overexpressing tricellulin were highly resistant to EPEC-induced barrier disruption. Confocal microscopy revealed the distribution of tricellulin into the plasma membrane of infected epithelial cells and confirmed the localization of EPEC aggregates in close proximity to tTJs. Moreover, infections with EPEC strains lacking genes encoding specific type III secreted effector proteins demonstrated a crucial role for the effector EspG1 in modulating tricellulin expression. Complementation studies suggest that the EspG-induced depletion of tricellulin is microtubule dependent. Overall, our results show that EPEC-induced epithelial barrier dysfunction is mediated in part by EspG1-induced microtubule-dependent depletion of tricellulin.

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