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

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

2018 ◽  
pp. 475-485 ◽  
Author(s):  
D.-Y. ZHAO ◽  
W.-X. ZHANG ◽  
Q.-Q. QI ◽  
X. LONG ◽  
X. LI ◽  
...  

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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Zhenxia Xu ◽  
Hu Tang ◽  
Fenghong Huang ◽  
Zhixian Qiao ◽  
Xu Wang ◽  
...  

Algal oil is rich in docosahexaenoic acid (DHA) and has various health benefits against human metabolic disorders and disease. This study aimed to investigate the effects of DHA algal oil on colonic inflammation and intestinal microbiota in dextran sulfate sodium (DSS)-induced colitis mice model. Male C57BL/6 mice was induced colitis by 2.5% DSS and followed by 2 weeks of treatment with algal oil (250 or 500 mg/kg/day). The colonic inflammation was assessed by colon macroscopic damage scores, and the degree of neutrophil infiltration was evaluated by measuring tissue-associated myeloperoxidase (MPO) activity in colonic mucosa. Tight junction proteins in the colonic tissue were measured by real-time PCR and western blot. Moreover, the intestinal microbiota and shot chain fatty acids (SCFAs) were estimated by bioinformatic analysis and GC, respectively. Colonic damage due to DSS treatment was significantly ameliorated by algal oil supplementation. In addition, algal oil significantly inhibited the increases of malondialdehyde (MDA) content, MPO activity, pro-inflammatory cytokines level and tight junction proteins expression in DSS-treated mice. Furthermore, supplementation of algal oil modulated the intestinal microbiota structure in DSS induced colitis mice by increasing the proportion of the unidentified_S24_7 and decreasing the relative abundance of unidentified_Ruminococcaceae, Clostridium and Roseburia. On the analysis of SCFAs, the caecal content of acetic acid, propionic acid, isobutyric acid, buturic, and the total SCFAs showed a significant increase in algal oil-administered mice. Together, these results suggested that algal oil rich in DHA inhibited the progress of DSS-induced colitis in mice by modulating the intestinal microbiota and metabolites and repairing the intestinal barrier, which may be applied in the development of therapeutics for intestinal inflammation.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Markus Utech ◽  
Rudolf Mennigen ◽  
Matthias Bruewer

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.


2019 ◽  
Vol 10 (2) ◽  
pp. 1235-1242 ◽  
Author(s):  
Caimei He ◽  
Jun Deng ◽  
Xin Hu ◽  
Sichun Zhou ◽  
Jingtao Wu ◽  
...  

Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases.


2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Zuojia Chen ◽  
Jialie Luo ◽  
Jian Li ◽  
Girak Kim ◽  
Eric S. Chen ◽  
...  

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.


2014 ◽  
Vol 62 (10) ◽  
pp. 2228-2232 ◽  
Author(s):  
Nathalie Nicod ◽  
Gemma Chiva-Blanch ◽  
Elena Giordano ◽  
Alberto Dávalos ◽  
Robert S. Parker ◽  
...  

2017 ◽  
Vol 44 (1) ◽  
pp. 333-344 ◽  
Author(s):  
Wenting Ma ◽  
Le Tao ◽  
Wei Zhang ◽  
Yinshen Zhu ◽  
Dongying Xue ◽  
...  

Background/Aims: Intestine-derived endotoxin is thought to play a role in the development of liver fibrosis. However, the pathological change in the intestine during liver fibrosis is still poorly understood. Here, we investigated the effects of Xia-yu-xue decoction (XYXD) on intestinal inflammation, apoptosis, and tight junction integrity in the carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Murine liver fibrosis was developed by CCI4 treatment three times per week over a 6-week period. The CCl4-treated mice were divided into two groups: the CCl4-water group (n=8, CCl4) and the CCl4-XYXD group (n=8, CCl4+XYXD). The CCl4+XYXD mice were treated with XYXD from the beginning of the first week. The expression of inflammatory cytokines and apoptotic molecules were examined using immunohistochemistry, real-time PCR, and western blot. The intestinal epithelial cell apoptosis was examined by TUNEL staining. The tight junction-related molecules, such as ZO-1, claudin, and occludin in the gut were measured by real-time PCR. Results: In CCl4-treated mice damage of the intestinal epithelia and infiltration of inflammatory cells into the lamina propria and muscular layer were observed. Proinflammatory markers MCP-1, TNF-α, CXCL11, IL-6, and CD68 were significantly increased in the intestinal epithelia in CCI4-treated mice. The expression of pro-apoptotic molecules including Fas and Bax was increased in the intestinal epithelia in CCI4-treated mice compared with that in control. The number of TUNEL-positive intestinal epithelial cells was also markedly increased in CCl4-treated mice. The expression of the tight junction proteins including ZO-1, claudin, and occludin was significantly decreased in CCI4-treated mice compared with that in control mice. Notably, XYXD treatment ameliorated increased inflammatory markers and apoptosis-related molecules and decreased tight-junction proteins in CCl4-treated mice. Conclusion: CCl4-treatment increased expression of proinflammatory cytokines and pro-apoptotic molecules and disrupted tight junction integrity in the intestine. XYXD treatment ameliorated intestinal inflammation, cell death, and tight junction disintegrity induced by CCl4 treatment, suggesting that XYXD inhibits CCl4-mediated liver fibrosis at least in part by ameliorating the intestinal epithelial damage.


2006 ◽  
Vol 44 (6) ◽  
pp. 898-902 ◽  
Author(s):  
M.-J. Kim ◽  
Y.-J. Kim ◽  
H.-J. Park ◽  
J.-H. Chung ◽  
K.-H. Leem ◽  
...  

2008 ◽  
Vol 45 (5) ◽  
pp. 386-394 ◽  
Author(s):  
Allison Walter ◽  
Nelly Etienne-Selloum ◽  
Mamadou Sarr ◽  
Modou Oumy Kane ◽  
Alain Beretz ◽  
...  

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