scholarly journals Differential Targeting of the E-Cadherin/β-Catenin Complex by Gram-Positive Probiotic Lactobacilli Improves Epithelial Barrier Function

2011 ◽  
Vol 78 (4) ◽  
pp. 1140-1147 ◽  
Author(s):  
Stephanie Hummel ◽  
Katharina Veltman ◽  
Christoph Cichon ◽  
Ulrich Sonnenborn ◽  
M. Alexander Schmidt
Keyword(s):  
Barrier Function ◽  
Epithelial Barrier ◽  
Gram Positive ◽  
Content Type ◽  
Epithelial Barrier Function ◽  
Beneficial Effects ◽  
Gastrointestinal Barrier ◽  
Probiotic Lactobacilli ◽  
Adherence Junction ◽  
Junction Proteins

ABSTRACTThe intestinal ecosystem is balanced by dynamic interactions between resident and incoming microbes, the gastrointestinal barrier, and the mucosal immune system. However, in the context of inflammatory bowel diseases (IBD), where the integrity of the gastrointestinal barrier is compromised, resident microbes contribute to the development and perpetuation of inflammation and disease. Probiotic bacteria have been shown to exert beneficial effects, e.g., enhancing epithelial barrier integrity. However, the mechanisms underlying these beneficial effects are only poorly understood. Here, we comparatively investigated the effects of four probiotic lactobacilli, namely,Lactobacillus acidophilus,L. fermentum,L. gasseri, andL. rhamnosus, in a T84 cell epithelial barrier model. Results of DNA microarray experiments indicating that lactobacilli modulate the regulation of genes encoding in particular adherence junction proteins such as E-cadherin and β-catenin were confirmed by quantitative reverse transcription-PCR (qRT-PCR). Furthermore, we show that epithelial barrier function is modulated by Gram-positive probiotic lactobacilli via their effect on adherence junction protein expression and complex formation. In addition, incubation with lactobacilli differentially influences the phosphorylation of adherence junction proteins and the abundance of protein kinase C (PKC) isoforms such as PKCδ that thereby positively modulates epithelial barrier function. Further insight into the underlying molecular mechanisms triggered by these probiotics might also foster the development of novel strategies for the treatment of gastrointestinal diseases (e.g., IBD).

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.

Beneficial effects of HDAC6 inhibition on airway epithelial barrier function

2019 ◽  
Author(s):  
Mia Collins ◽  
Jenny Horndahl ◽  
Rebecka Svärd ◽  
Theresa Andreasson ◽  
Anders Cavallin ◽  
...  
Keyword(s):  
Barrier Function ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Epithelial Barrier Function ◽  
Beneficial Effects

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.

scholarly journals The Role of Cell Surface Architecture of Lactobacilli in Host-Microbe Interactions in the Gastrointestinal Tract

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Ranjita Sengupta ◽  
Eric Altermann ◽  
Rachel C. Anderson ◽  
Warren C. McNabb ◽  
Paul J. Moughan ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Cell Surface ◽  
Barrier Function ◽  
Stress Factors ◽  
Epithelial Barrier ◽  
Protective Effects ◽  
Epithelial Barrier Function ◽  
Beneficial Effects ◽  
The Face ◽  
Host Microbe Interactions

Lactobacillusspecies can exert health promoting effects in the gastrointestinal tract (GIT) through many mechanisms, which include pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Different species of the genusLactobacilluscan evoke different responses in the host, and not all strains of the same species can be considered beneficial. Strain variations may be related to diversity of the cell surface architecture of lactobacilli and the bacteria's ability to express certain surface components or secrete specific compounds in response to the host environment. Lactobacilli are known to modify their surface structures in response to stress factors such as bile and low pH, and these adaptations may help their survival in the face of harsh environmental conditions encountered in the GIT. In recent years, multiple cell surface-associated molecules have been implicated in the adherence of lactobacilli to the GIT lining, immunomodulation, and protective effects on intestinal epithelial barrier function. Identification of the relevant bacterial ligands and their host receptors is imperative for a better understanding of the mechanisms through which lactobacilli exert their beneficial effects on human health.

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 Ganglioside Alters Phospholipase Trafficking, Inhibits NF-κB Assembly, and Protects Tight Junction Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
John J. Miklavcic ◽  
Qun Li ◽  
Jordan Skolnick ◽  
Alan B. R. Thomson ◽  
Vera C. Mazurak ◽  
...  
Keyword(s):  
Barrier Function ◽  
Animal Studies ◽  
Milk Powder ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function ◽  
Beneficial Effects ◽  
Intestinal Integrity ◽  
Inflammatory Stimuli

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health.Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. Gut barrier integrity was assessed by electron microscopy, epithelial barrier function was examined by measuring transepithelial electric resistance, and content of HBD-2, IL-23, NF-κB, and sPLA2 was assessed by ELISA.Results: Ganglioside attenuated the decrease in integrity of tight junctions induced by pro-inflammatory stimuli and improved epithelial barrier function (P < 0.05). Ganglioside decreased the basolateral secretion of sPLA2 (P ≤ 0.05), lowered HBD-2 and IL-23 levels (P ≤ 0.05), and inhibited NF-κB activation (P ≤ 0.05).Conclusions: In summary, the present study indicates that ganglioside GD3 improves intestinal integrity by altering sPLA2 trafficking, and the production of pro-inflammatory mediators is mitigated by decreasing assembly of the NF-κB complex. Dietary gangliosides may have promising potential beneficial effects in IBD as decreased inflammatory signaling, improved intestinal integrity, and maintenance of epithelial barrier function have been demonstrated in vitro.

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