A SNP of Bacterial Blc Disturbs Gut Lysophospholipid Homeostasis and Induces Inflammation Through Epithelial Barrier Disruption

2019 ◽  
Author(s):  
Dayuan Zou ◽  
Di Chen ◽  
Jingwen Pei ◽  
Jianfeng Lan ◽  
Hong Sang ◽  
...  
Keyword(s):  
Epithelial Barrier ◽  
Barrier Disruption

scholarly journals Pectin limits epithelial barrier disruption by Citrobacter rodentium through anti-microbial effects

2021 ◽  
Author(s):  
M. Beukema ◽  
K. Ishisono ◽  
J. de Waard ◽  
M. M. Faas ◽  
P. de Vos ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Barrier ◽  
Citrobacter Rodentium ◽  
Barrier Dysfunction ◽  
Antimicrobial Effects ◽  
Barrier Disruption ◽  
Microbial Effects

Pectins inhibit the growth of C. rodentium in vitro, preventing attachment of C. rodentium to CMT93 epithelial cells. Through these antimicrobial effects, pectins protect the epithelium from C. rodentium-induced barrier dysfunction and damage.

scholarly journals A Novel Pharmacological Approach to Enhance the Integrity and Accelerate Restitution of the Intestinal Epithelial Barrier

2020 ◽  
Vol 26 (9) ◽  
pp. 1340-1352
Author(s):  
Xuelei Cao ◽  
Lei Sun ◽  
Susana Lechuga ◽  
Nayden G Naydenov ◽  
Alex Feygin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cell ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Cell Monolayers ◽  
Barrier Disruption ◽  
Epithelial Cell Monolayers ◽  
Immunofluorescence Labeling ◽  
E Cadherin

Abstract Background Disruption of the gut barrier is an essential mechanism of inflammatory bowel diseases (IBDs) contributing to the development of mucosal inflammation. A hallmark of barrier disruption is the disassembly of epithelial adherens junctions (AJs) driven by decreased expression of a major AJ protein, E-cadherin. A group of isoxazole compounds, such as E-cadherin-upregulator (ECU) and ML327, were previously shown to stimulate E-cadherin expression in poorly differentiated human cancer cells. This study was designed to examine whether these isoxazole compounds can enhance and protect model intestinal epithelial barriers in vitro. Methods The study was conducted using T84, SK-CO15, and HT-29 human colonic epithelial cell monolayers. Disruption of the epithelial barrier was induced by pro-inflammatory cytokines, tumor necrosis factor-α, and interferon-γ. Barrier integrity and epithelial junction assembly was examined using different permeability assays, immunofluorescence labeling, and confocal microscopy. Epithelial restitution was analyzed using a scratch wound healing assay. Results E-cadherin-upregulator and ML327 treatment of intestinal epithelial cell monolayers resulted in several barrier-protective effects, including reduced steady-state epithelial permeability, inhibition of cytokine-induced barrier disruption and junction disassembly, and acceleration of epithelial wound healing. Surprisingly, these effects were not due to upregulation of E-cadherin expression but were mediated by multiple mechanisms including inhibition of junction protein endocytosis, attenuation of cytokine-induced apoptosis, and activation of promigratory Src and AKT signaling. Conclusions Our data highlight ECU and ML327 as promising compounds for developing new therapeutic strategies to protect the integrity and accelerate the restitution of the intestinal epithelial barrier in IBD and other inflammatory disorders.

Jejunal epithelial barrier disruption triggered by reactive oxygen species in early SIV infected rhesus macaques

2021 ◽  
Author(s):  
Xue-Hui Wang ◽  
Tian-Zhang Song ◽  
Hong-Yi Zheng ◽  
Yi-Hui Li ◽  
Yong-Tang Zheng
Keyword(s):  
Reactive Oxygen Species ◽  
Rhesus Macaques ◽  
Reactive Oxygen ◽  
Epithelial Barrier ◽  
Oxygen Species ◽  
Barrier Disruption

scholarly journals Cleavage of E-cadherin by porcine respiratory bacterial pathogens facilitates airway epithelial barrier disruption and bacterial paracellular transmigration

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 2296-2313
Author(s):  
Qi Cao ◽  
Wenbin Wei ◽  
Huan Wang ◽  
Zesong Wang ◽  
Yujin Lv ◽  
...  
Keyword(s):  
Bacterial Pathogens ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Disruption ◽  
Porcine Respiratory ◽  
E Cadherin

scholarly journals A Micro-engineered Human Colon Intestine-Chip Platform to Study Leaky Barrier

2020 ◽  
Author(s):  
Athanasia Apostolou ◽  
Rohit A. Panchakshari ◽  
Antara Banerjee ◽  
Dimitris V. Manatakis ◽  
Maria D. Paraskevopoulou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Unmet Need ◽  
Intestinal Barrier ◽  
Human Colon ◽  
Epithelial Barrier ◽  
Host Immune System ◽  
Intestinal Epithelial ◽  
Barrier Disruption ◽  
Interleukin 22

ABSTRACTThe intestinal epithelial barrier supports the symbiotic relationship between the microbiota colonizing the intestinal epithelium and the host immune system to maintain homeostasis. Leaky barrier is increasingly recognized as part of the pathogenesis of a number of chronic conditions in addition to inflammatory and infectious diseases. As our understanding on the regulation of the barrier remains limited, effective therapeutic targeting for the compromised barrier is still an unmet need. Here we combined advancements on the organoids and Organ-on-Chip technologies to establish a micro-engineered Colon Intestine-Chip for studying development and regulation of the human intestinal barrier. Our data demonstrate the significance of the endothelium in co-culture with the epithelial cells within a tissue-relevant microenvironment for the establishment of a tight epithelial barrier of polarized cells. Pathway analysis of the RNA sequencing (RNA-Seq), revealed significant upregulation of mechanisms relevant to the maturation of the intestinal epithelium in organoid-derived epithelial cells in co-culture with endothelium as compared to organoids maintained in suspension. We provide evidence that the Colon Intestine-Chip platform responds to interferon gamma (IFNγ), a prototype cytokine utilized to model inflammation-induced barrier disruption, by induction of apoptosis and reorganization of the apical junctional complexes as shown with other systems. We also describe the mechanism of action of interleukin 22 (IL-22) on mature, organoid-derived intestinal epithelial cells that is consistent with barrier disruption. Overall we propose the Colon Intestine-Chip as a promising human organoid-derived platform to decipher mechanisms driving the development of leaky gut in patients and enable their translation for this unmet medical need.

Citrobacter rodentium Requires Intestinal Neural Wiskott-Aldrich Syndrome Protein (N-WASp) for Actin Pedestal Formation, Colonization and Epithelial Barrier Disruption In Vivo

2011 ◽  
Vol 140 (5) ◽  
pp. S-646
Author(s):  
John J. Garber ◽  
Hai Ning Shi ◽  
Deanna D. Nguyen ◽  
Michel H. Maillard ◽  
Emily Mallick ◽  
...  
Keyword(s):  
Epithelial Barrier ◽  
Citrobacter Rodentium ◽  
Wiskott Aldrich Syndrome ◽  
Barrier Disruption ◽  
Syndrome Protein ◽  
Pedestal Formation

scholarly journals HMGB1-downregulated angulin-1/LSR induces epithelial barrier disruption via claudin-2 and cellular metabolism via AMPK in airway epithelial Calu-3 cells

2020 ◽  
Vol 527 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Yuki Kodera ◽  
Hirofumi Chiba ◽  
Takumi Konno ◽  
Takayuki Kohno ◽  
Hiroki Takahashi ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Disruption

Vasoactive intestinal peptide prevents PKCε-induced intestinal epithelial barrier disruption during EPEC infection

2015 ◽  
Vol 308 (5) ◽  
pp. G389-G402 ◽  
Author(s):  
V. Morampudi ◽  
V. S. Conlin ◽  
U. Dalwadi ◽  
X. Wu ◽  
K. C. Marshall ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Critical Role ◽  
Term Treatment ◽  
Epithelial Barrier ◽  
Protective Effects ◽  
Short Term Treatment ◽  
Barrier Integrity ◽  
Barrier Disruption ◽  
Long Term Treatment

We previously showed that vasoactive intestinal peptide (VIP) protects against bacterial pathogen-induced epithelial barrier disruption and colitis, although the mechanisms remain poorly defined. The aim of the current study was to identify cellular pathways of VIP-mediated protection with use of pharmacological inhibitors during enteropathogenic Escherichia coli (EPEC) infection of Caco-2 cell monolayers and during Citrobacter rodentium-induced colitis. EPEC-induced epithelial barrier disruption involved the PKC pathway but was independent of functional cAMP, Rho, and NF-κB pathways. VIP mediated its protective effects by inhibiting EPEC-induced PKC activity and increasing expression of the junctional protein claudin-4. Short-term treatment with TPA, which is known to activate PKC, was inhibited by VIP pretreatment, while PKC degradation via long-term treatment with TPA mimicked the protective actions of VIP. Immunostaining for specific PKC isotypes showed upregulated expression of PKCθ and PKCε during EPEC infection. Treatment with specific inhibitors revealed a critical role for PKCε in EPEC-induced barrier disruption. Furthermore, activation of PKCε and loss of barrier integrity correlated with claudin-4 degradation. In contrast, inhibition of PKCε by VIP pretreatment or the PKCε inhibitor maintained membrane-bound claudin-4 levels, along with barrier function. Finally, in vivo treatment with the PKCε inhibitor protected mice from C. rodentium-induced colitis. In conclusion, EPEC infection increases intracellular PKCε levels, leading to decreased claudin-4 levels and compromising epithelial barrier integrity. VIP inhibits PKCε activation, thereby attenuating EPEC-induced barrier disruption.

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