scholarly journals Endocytosis and Recycling of Tight Junction Proteins in Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Markus Utech ◽  
Rudolf Mennigen ◽  
Matthias Bruewer
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Critical Function ◽  
Recycling Endosomes ◽  
Inflammatory Conditions ◽  
Apical Junctional Complex ◽  
Junction Proteins

A critical function of the epithelial lining is to form a barrier that separates luminal contents from the underlying interstitium. This barrier function is primarily regulated by the apical junctional complex (AJC) consisting of tight junctions (TJs) and adherens junctions (AJs) and is compromised under inflammatory conditions. In intestinal epithelial cells, proinflammatory cytokines, for example, interferon-gamma (IFN-γ), induce internalization of TJ proteins by endocytosis. Endocytosed TJ proteins are passed into early and recycling endosomes, suggesting the involvement of recycling of internalized TJ proteins. This review summarizes mechanisms by which TJ proteins under inflammatory conditions are internalized in intestinal epithelial cells and point out comparable mechanism in nonintestinal epithelial cells.

scholarly journals Brain-Derived Neurotrophic Factor Modulates Intestinal Barrier by Inhibiting Intestinal Epithelial Cells Apoptosis in Mice

2018 ◽  
pp. 475-485 ◽  
Author(s):  
D.-Y. ZHAO ◽  
W.-X. ZHANG ◽  
Q.-Q. QI ◽  
X. LONG ◽  
X. LI ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Colonic Mucosa ◽  
Caspase 3 ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Intestinal Barrier Integrity ◽  
Junction Proteins ◽  
Active Caspase

We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF+/+ mice and BDNF+/- mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF+/+ mice, BDNF+/- mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF+/- mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF+/- mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties.

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.

Red wine extract preserves tight junctions in intestinal epithelial cells under inflammatory conditions: implications for intestinal inflammation

2019 ◽  
Vol 10 (3) ◽  
pp. 1364-1374 ◽  
Author(s):  
Carla Nunes ◽  
Víctor Freitas ◽  
Leonor Almeida ◽  
João Laranjinha
Keyword(s):  
Red Wine ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Inflammatory Conditions ◽  
Inflammatory Stimuli ◽  
Wine Polyphenols ◽  
Red Wine Polyphenols ◽  
Junction Proteins

Red wine polyphenols protect the intestinal barrier against inflammatory stimuli by modulating the gene expression of key tight junction proteins.

scholarly journals Baicalin-Induced Autophagy Preserved LPS-Stimulated Intestinal Cells from Inflammation and Alterations of Paracellular Permeability

2021 ◽  
Vol 22 (5) ◽  
pp. 2315
Author(s):  
Valentina Rizzo ◽  
Nadia Ferlazzo ◽  
Monica Currò ◽  
Gaetano Isola ◽  
Marco Matarese ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Paracellular Permeability ◽  
Autophagic Flux ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn’s disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. However, few studies have evaluated BA effects on autophagic signaling in epithelial cell response to inflammatory stimuli. To explore possible beneficial effects of BA, HT-29 cells were exposed to lipopolysaccharide (LPS), in presence or absence of BA, for 4 h. We evaluated mRNA levels of autophagy-related genes and cytokines, triggering inflammatory response. Furthermore, the expression of claudin 1, involved in the regulation of paracellular permeability was analyzed. BA treatment repressed LPS-induced expression of TNF-α and IL-1β. The down-regulation of autophagy-related genes induced by LPS was counteracted by cell pretreatment with BA. Under these conditions, BA reduced the NF-κB activation caused by LPS. Also, BA restored mRNA and protein levels of claudin 1, which were reduced by LPS. In conclusion, in intestinal epithelial cells BA regulates the NF-κB activation and modulates both autophagic and inflammatory processes, leading to an improvement of paracellular permeability. These results suggest that the anti-inflammatory effects of BA can be associated to the regulation of autophagic flux.

scholarly journals alpha-Actinin localization in the junctional complex of intestinal epithelial cells.

1979 ◽  
Vol 80 (1) ◽  
pp. 203-210 ◽  
Author(s):  
S W Craig ◽  
J V Pardo
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Sodium Dodecyl ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Membrane Structures ◽  
Apical Portion ◽  
Chicken Gizzard ◽  
Subunit Molecular Weight ◽  
Polygonal Pattern

We have used antibody to chicken gizzard alpha-actinin to identify and localize this molecule in chicken intestinal epithelium. The antibody binds only to alpha-actinin when tested against a crude extract of chicken gizzard. Extracts of purified epithelial cells contain a molecule which has a subunit molecular weight of 100,000 on sodium dodecyl sulphate gels and which is able to inhibit the interaction of alpha-actinin antibody and 125I-labeled chicken gizzard alpha-actinin. By indirect immunofluorescence, alpha-actinin is localized in the apical portion of chicken intestinal epithelial cells. Ethanol-fixed cryostat sections of intestine taken through the apical portion of the epithelial cells and in a plane perpendicular to the long axis of the cells show that alpha-actinin is organized in a polygonal pattern which corresponds to the outlines of the polygonally packed epithelial cells. We interpret the data as indicating that alpha-actinin is a component of the tight junction (zonula occludens) and/or the belt desmosome (zonula adherens), both of which are membrane structures known to encircle the cell and to be confined to its apical portion.

scholarly journals Localization of capping protein in chicken epithelial cells by immunofluorescence and biochemical fractionation.

1992 ◽  
Vol 118 (2) ◽  
pp. 335-346 ◽  
Author(s):  
D A Schafer ◽  
M S Mooseker ◽  
J A Cooper
Keyword(s):  
Epithelial Cells ◽  
Actin Filaments ◽  
Intestinal Epithelial Cells ◽  
Sensory Epithelium ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Capping Protein ◽  
Pigmented Epithelium ◽  
Biochemical Fractionation ◽  
Junctional Complexes

We have localized capping protein in epithelial cells of several chicken tissues using affinity-purified polyclonal antibodies and immunofluorescence. Capping protein has a distribution in each tissue coincident with proteins of the cell-cell junctional complex, which includes the zonula adherens, zonula occludens, and desmosome. "En face" views of the epithelial cells showed capping protein distributed in a polygonal pattern coincident with cell boundaries in intestinal epithelium, sensory epithelium of the cochlea, and the pigmented epithelium of the retina and at regions of cell-cell contact between chick embryo kidney cells in culture. "Edge-on" views obtained by confocal microscopy of intact single intestinal epithelial cells and of retinal pigmented epithelium showed that capping protein is located in the apical region of the epithelial cells coincident with the junctional complexes. These images do not resolve the individual types of junctions of the junctional complex. Immunolabeling of microvilli or stereocilia was faint or not detectable. Capping protein was also detected in the cytoplasm of intact intestinal epithelial cells and in nuclei of cells in the pigmented retina and in the kidney cell cultures, but not in nuclei of cells of the intestinal epithelium or sensory epithelium. Biochemical fractionation of isolated intestinal epithelial cells shows capping protein in the brush border fraction, which contains the junctional complexes, and in the soluble fraction. These results are consistent with the results of the immunolabeling experiments. Highly purified microvilli of the brush borders also contained capping protein; this result was unexpected based on the low intensity of immunofluorescence staining of microvilli and stereocilia. The microvilli were not contaminated with junctional complexes, as defined by the absence of several markers for cell junctions. The cause and significance of this discrepancy is not certain at this time. Since capping protein binds the barbed end of actin filaments in vitro, we hypothesize that capping protein is bound to the barbed ends of actin filaments associated with one or more of the junctions of the junctional complex.

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