scholarly journals Influence of phenolics on epithelial barrier function and the expression of tight junction proteins in Caco-2 cells

2013 ◽  
Vol 72 (OCE4) ◽  
Author(s):  
P. Kullamethee ◽  
D. M. Commane ◽  
I. R. Rowland
Keyword(s):  
Tight Junction ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

scholarly journals Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function

2011 ◽  
Vol 301 (1) ◽  
pp. L40-L49 ◽  
Author(s):  
Leslie A. Mitchell ◽  
Christian E. Overgaard ◽  
Christina Ward ◽  
Susan S. Margulies ◽  
Michael Koval
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Alveolar Epithelial ◽  
Junction Proteins

Alveolar barrier function depends critically on the claudin family tight junction proteins. Of the major claudins expressed by alveolar epithelial cells, claudin (Cldn)-3 and Cldn-4 are the most closely related by amino acid homology, yet they differ dramatically in the pattern of expression. Previously published reports have shown that Cldn-3 is predominantly expressed by type II alveolar epithelial cells; Cldn-4 is expressed throughout the alveolar epithelium and is specifically upregulated in response to acute lung injury. Using primary rat alveolar epithelial cells transduced with yellow fluorescent protein-tagged claudin constructs, we have identified roles for Cldn-3 and Cldn-4 in alveolar epithelial barrier function. Surprisingly, increasing expression of Cldn-3 decreased alveolar epithelial barrier function, as assessed by transepithelial resistance and dye flux measurements. Conversely, increasing Cldn-4 expression improved alveolar epithelial transepithelial resistance compared with control cells. Other alveolar epithelial tight junction proteins were largely unaffected by increased expression of Cldn-3 and Cldn-4. Taken together, these results demonstrate that, in the context of the alveolar epithelium, Cldn-3 and Cldn-4 have different effects on paracellular permeability, despite significant homology in their extracellular loop domains.

Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells

2005 ◽  
Vol 288 (6) ◽  
pp. G1159-G1169 ◽  
Author(s):  
Xin Guo ◽  
Jaladanki N. Rao ◽  
Lan Liu ◽  
Tongtong Zou ◽  
Kaspar M. Keledjian ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Integral Membrane Protein ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

Occludin is an integral membrane protein that forms the sealing element of tight junctions and is critical for epithelial barrier function. Polyamines are implicated in multiple signaling pathways driving different biological functions of intestinal epithelial cells (IEC). The present study determined whether polyamines are involved in expression of occludin and play a role in intestinal epithelial barrier function. Studies were conducted in stable Cdx2-transfected IEC-6 cells (IEC-Cdx2L1) associated with a highly differentiated phenotype. Polyamine depletion by α-difluoromethylornithine (DFMO) decreased levels of occludin protein but failed to affect expression of its mRNA. Other tight junction proteins, zonula occludens (ZO)-1, ZO-2, claudin-2, and claudin-3, were also decreased in polyamine-deficient cells. Decreased levels of tight junction proteins in DFMO-treated cells were associated with dysfunction of the epithelial barrier, which was overcome by exogenous polyamine spermidine. Decreased levels of occludin in polyamine-deficient cells was not due to the reduction of intracellular-free Ca2+ concentration ([Ca2+]cyt), because either increased or decreased [Ca2+]cyt did not alter levels of occludin in the presence or absence of polyamines. The level of newly synthesized occludin protein was decreased by ∼70% following polyamine depletion, whereas its protein half-life was reduced from ∼120 min in control cells to ∼75 min in polyamine-deficient cells. These findings indicate that polyamines are necessary for the synthesis and stability of occludin protein and that polyamine depletion disrupts the epithelial barrier function, at least partially, by decreasing occludin.

Bryostatin-1 enhances barrier function in T84 epithelia through PKC-dependent regulation of tight junction proteins

2003 ◽  
Vol 285 (2) ◽  
pp. C300-C309 ◽  
Author(s):  
James Yoo ◽  
Anthony Nichols ◽  
Joshua Mammen ◽  
Isabel Calvo ◽  
Jaekyung C. Song ◽  
...  
Keyword(s):  
Tight Junction ◽  
Barrier Function ◽  
Insoluble Fraction ◽  
Junctional Complex ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Bryostatin 1 ◽  
Epithelial Barrier Function ◽  
Pkc Inhibitor ◽  
Junction Proteins

Protein kinase C (PKC) is known to regulate epithelial barrier function. However, the effect of specific PKC isozymes, and their mechanism of action, are largely unknown. We determined that the nonphorbol ester PKC agonist bryostatin-1 increased transepithelial electrical resistance (TER), a marker of barrier function, in confluent T84 epithelia. Bryostatin-1, which has been shown to selectively activate PKC-α, -ϵ, and -δ ( 34 ), was associated with a shift in the subcellular distribution of the tight junction proteins claudin-1 and ZO-2 from a detergent-soluble fraction into a detergent-insoluble fraction. Bryostatin-1 also led to the appearance of a higher-molecular-weight form of occludin previously shown to correspond to protein phosphorylation. These changes were attenuated by the conventional and novel PKC inhibitor Gö-6850 but not the conventional PKC inhibitor Gö-6976 or the PKC-δ inhibitor röttlerin, implicating a novel isozyme, likely PKC-ϵ. The results suggest that enhanced epithelial barrier function induced by bryostatin-1 involves a PKC-ϵ-dependent signaling pathway leading to recruitment of claudin-1 and ZO-2, and phosphorylation of occludin, into the tight junctional complex.

scholarly journals Meprins Affect Epithelial Barrier Function by Cleaving Tight Junction Proteins

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Jialing Bao ◽  
Stephanie Cornely ◽  
Gail Matters ◽  
S.Gaylen Bradley ◽  
Judith Bond
Keyword(s):  
Tight Junction ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

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.

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.

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.

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