scholarly journals Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation

2015 ◽  
Vol 135 (7) ◽  
pp. 1790-1800 ◽  
Author(s):  
Caroline Stremnitzer ◽  
Krisztina Manzano-Szalai ◽  
Anna Willensdorfer ◽  
Philipp Starkl ◽  
Mario Pieper ◽  
...  
Keyword(s):  
Tight Junction ◽  
Enzymatic Activity ◽  
Human Keratinocytes ◽  
Tight Junction Proteins ◽  
Tlr4 Activation ◽  
Junction Proteins

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals MicroRNA-30a regulates acute cerebral ischemia-induced blood–brain barrier damage through ZnT4/zinc pathway

2020 ◽  
pp. 0271678X2092678 ◽  
Author(s):  
Peng Wang ◽  
Rong Pan ◽  
John Weaver ◽  
Mengjie Jia ◽  
Xue Yang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Blood Brain ◽  
Acute Cerebral Ischemia ◽  
Junction Proteins

The mechanism of early blood–brain barrier (BBB) disruption after stroke has been intensively studied but still not fully understood. Here, we report that microRNA-30a (miR-30a) could mediate BBB damage using both cellular and animal models of ischemic stroke. In the experiments in vitro, inhibition of miR-30a decreased BBB permeability, prevented the degradation of tight junction proteins, and reduced intracellular free zinc in endothelial cells. We found that the zinc transporter ZnT4 was a direct target of negative regulation by miR-30a, and ZnT4/zinc signaling pathway contributed significantly to miR-30a-mediated BBB damage. Consistent with these in vitro findings, treatment with miR-30a inhibitor reduced zinc accumulation, increased the expression of ZnT4, and prevented the loss of tight junction proteins in microvessels of ischemic animals. Furthermore, inhibition of miR-30a, even at 90 min post onset of middle cerebral artery occlusion, prevented BBB damage, reduced infarct volume, and ameliorated neurological deficits. Together, our findings provide novel insights into the mechanisms of cerebral ischemia-induced BBB disruption and indicate miR-30a as a regulator of BBB function that can be an effective therapeutic target for ischemic stroke.

scholarly journals Intestinal epithelial barrier function and tight junction proteins with heat and exercise

2016 ◽  
Vol 120 (6) ◽  
pp. 692-701 ◽  
Author(s):  
Karol Dokladny ◽  
Micah N. Zuhl ◽  
Pope L. Moseley
Keyword(s):  
Heat Stress ◽  
Tight Junction ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Tight Junction ◽  
Junction Proteins

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise.

scholarly journals Allyl Isothiocyanate Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mouse by Enhancing Tight Junction and Mucin Expression

2018 ◽  
Vol 19 (7) ◽  
pp. 2025 ◽  
Author(s):  
Min Kim ◽  
Seungho Choi ◽  
Sun Kim ◽  
Yeo Yoon ◽  
Ju-Hee Kang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Cell Line ◽  
Allyl Isothiocyanate ◽  
In Vivo Studies ◽  
Intestinal Barrier Function ◽  
Tight Junction Proteins ◽  
Mucin Expression ◽  
Junction Proteins

Inflammatory bowel disease (IBD) is characterized by chronic or recurrent inflammation of the gastrointestinal tract. Even though the current strategies to treat IBD include anti-inflammatory drugs and immune modulators, these treatments have side-effects. New strategies are, therefore, required to overcome the limitations of the therapies. In this study, we investigated the anti-colitic effects of allyl isothiocyanate (AITC), which is an active ingredient present in Wasabia japonica. The DSS-induced colitis model in the mouse was used to mimic human IBD and we observed that AITC treatment ameliorated the severity of colitis. We further studied the mechanism involved to ameliorate the colitis. To investigate the involvement of AITC on the intestinal barrier function, the effect on the intercellular tight junction was evaluated in the Caco-2 cell line while mucin expression was assessed in the LS174T cell line. AITC positively regulated tight junction proteins and mucin 2 (MUC2) against DSS-induced damage or depletion. Our data of in vivo studies were also consistent with the in vitro results. Furthermore, we observed that MUC2 increased by AITC is dependent on ERK signaling. In conclusion, we propose that AITC can be considered as a new strategy for treating IBD by modulating tight junction proteins and mucin.

Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated withCitrobacter rodentium-induced colitis

2009 ◽  
Vol 297 (4) ◽  
pp. G735-G750 ◽  
Author(s):  
V. S. Conlin ◽  
X. Wu ◽  
C. Nguyen ◽  
C. Dai ◽  
B. A. Vallance ◽  
...  
Keyword(s):  
Tight Junction ◽  
Myosin Light Chain ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

Attaching and effacing bacterial pathogens attach to the apical surface of epithelial cells and disrupt epithelial barrier function, increasing permeability and allowing luminal contents access to the underlying milieu. Previous in vitro studies demonstrated that the neuropeptide vasoactive intestinal peptide (VIP) regulates epithelial paracellular permeability, and the high concentrations and close proximity of VIP-containing nerve fibers to intestinal epithelial cells would support such a function in vivo. The aim of this study was to examine whether VIP treatment modulated Citrobacter rodentium-induced disruption of intestinal barrier integrity and to identify potential mechanisms of action. Administration of VIP had no effect on bacterial attachment although histopathological scoring demonstrated a VIP-induced amelioration of colitis-induced epithelial damage compared with controls. VIP treatment prevented the infection-induced increase in mannitol flux a measure of paracellular permeability, resulting in levels similar to control mice, and immunohistochemical studies demonstrated that VIP prevented the translocation of tight junction proteins: zonula occludens-1, occludin, and claudin-3. Enteropathogenic Escherichia coli (EPEC) infection of Caco-2 monolayers confirmed a protective role for VIP on epithelial barrier function. VIP prevented EPEC-induced increase in long myosin light chain kinase (MLCK) expression and myosin light chain phosphorylation (p-MLC). Furthermore, MLCK inhibition significantly attenuated bacterial-induced epithelial damage both in vivo and in vitro. In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation.

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle1

2017 ◽  
Vol 95 (3) ◽  
pp. 1313-1324 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals A novel in vitro platform for the study of SN38-induced mucosal damage and the development of Toll-like receptor 4-targeted therapeutic options

2016 ◽  
Vol 241 (13) ◽  
pp. 1386-1394 ◽  
Author(s):  
Hannah R Wardill ◽  
Rachel J Gibson ◽  
Ysabella ZA Van Sebille ◽  
Kate R Secombe ◽  
Richard M Logan ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Mucosal Damage ◽  
Toll Like Receptor ◽  
Tight Junction Proteins ◽  
T84 Cells ◽  
Toll Like Receptor 4 ◽  
Transmission Electron ◽  
Junction Proteins

Tight junction and epithelial barrier disruption is a common trait of many gastrointestinal pathologies, including chemotherapy-induced gut toxicity. Currently, there are no validated in vitro models suitable for the study of chemotherapy-induced mucosal damage that allow paralleled functional and structural analyses of tight junction integrity. We therefore aimed to determine if a transparent, polyester membrane insert supports a polarized T84 monolayer with the phenotypically normal tight junctions. T84 cells (passage 5–15) were seeded into either 0.6 cm2, 0.4 µm pore mixed-cellulose transwell hanging inserts or 1.12 cm2, 0.4 µm pore polyester transwell inserts at varying densities. Transepithelial electrical resistance was measured daily to assess barrier formation. Immunofluoresence for key tight junction proteins (occludin, zonular occludens-1, claudin-1) and transmission electron microscopy were performed to assess tight junction integrity, organelle distribution, and polarity. Reverse transcription-polymerase chain reaction was performed to determine expression of toll-like receptor 4 (TLR4). Liquid chromatography was also conducted to assess SN38 degradation in this model. Polyester membrane inserts support a polarized T84 phenotype with functional tight junctions in vitro. Transmission electron microscopy indicated polarity, with apico-laterally located tight junctions. Immunofluorescence showed membranous staining for all tight junction proteins. No internalization was evident. T84 cells expressed TLR4, although this was significantly lower than levels seen in HT29 cells ( P = .0377). SN38 underwent more rapid degradation in the presence of cells (−76.04 ± 1.86%) compared to blank membrane (−48.39 ± 4.01%), indicating metabolic processes. Polyester membrane inserts provide a novel platform for paralleled functional and structural analysis of tight junction integrity in T84 monolayers. T84 cells exhibit the unique ability to metabolize SN38 as well as expressing TLR4, making this an excellent platform to study clinically relevant therapeutic interventions for SN38-induced mucosal damage by targeting TLR4.

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