scholarly journals Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Dacheng Wu ◽  
Keyan Wu ◽  
Qingtian Zhu ◽  
Weiming Xiao ◽  
Qing Shan ◽  
...  
Keyword(s):  
Tight Junction ◽  
Nlrp3 Inflammasome ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Acute Injury ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tight Junction Proteins ◽  
Acute Colitis ◽  
Junction Proteins

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Digestion of epithelial tight junction proteins by the commensal Clostridium perfringens

2013 ◽  
Vol 305 (10) ◽  
pp. G740-G748 ◽  
Author(s):  
Mihaela Pruteanu ◽  
Fergus Shanahan
Keyword(s):  
Epithelial Cell ◽  
Tight Junction ◽  
Clostridium Perfringens ◽  
Culture Supernatant ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Epithelial Tight Junction ◽  
Junction Proteins ◽  
E Cadherin

The enteric microbiota contributes to the pathogenesis of inflammatory bowel disease, but the pathways involved and bacterial participants may vary in different hosts. We previously reported that some components of the human commensal microbiota, particularly Clostridium perfringens ( C. perfringens), have the proteolytic capacity for host matrix degradation and reduce transepithelial resistance. Here, we examined the C. perfringens-derived proteolytic activity against epithelial tight junction proteins using human intestinal epithelial cell lines. We showed that the protein levels of E-cadherin, occludin, and junctional adhesion molecule 1 decrease in colonic cells treated with C. perfringens culture supernatant. E-cadherin ectodomain shedding in C. perfringens-stimulated intestinal epithelial cells was detected with antibodies against the extracellular domain of E-cadherin, and we demonstrate that this process occurs in a time- and dose-dependent manner. In addition, we showed that the filtered sterile culture supernatant of C. perfringens has no cytotoxic activity on the human intestinal cells at the concentrations used in this study. The direct cleavage of E-cadherin by the proteases from the C. perfringens culture supernatant was confirmed by C. perfringens supernatant-induced in vitro degradation of the human recombinant E-cadherin. We conclude that C. perfringens culture supernatant mediates digestion of epithelial cell junctional proteins, which is likely to enable access to the extracellular matrix components by the paracellular pathway.

scholarly journals Choline Treatment Activates NLRP3 Inflammasome Formation and Leads to Endothelial Dysfunction in Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 44-44
Author(s):  
Saisudha Koka ◽  
Goverdhan Puchchakayala ◽  
Krishna Boini
Keyword(s):  
Endothelial Dysfunction ◽  
Tight Junction ◽  
Real Time ◽  
Nlrp3 Inflammasome ◽  
Real Time Pcr ◽  
Inflammatory Markers ◽  
Carotid Arteries ◽  
Pcr Analysis ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Objectives Choline and other trimethylamine-containing nutrients are metabolized by gut microbiota into Trimethylamine N-oxide (TMAO), which is involved in the pathogenesis of various cardiovascular diseases. The present study was designed to investigate the relation between dietary choline and endothelial dysfunction in mice. Methods Nlrp3 +/+ and Nlrp3 −/− mice were treated with 3% choline chloride in drinking water for 6 months. Plasma concentration of TMAO levels were measured after the treatment. Cardiac and endothelial dysfunction were monitored using echocardiography. Vascular permeability was measured by Evans blue dye perfusion. Confocal microscopy was used to detect the co-localization of Nlrp3 inflammasome components. Caspase-1 activity was measured by colorimetric assay and IL-1β production was measured using ELISA. Western blotting was used to measure tight-junction proteins. Real time PCR analysis was used to determine the TLR-4 and inflammatory markers (ICAM and VCAM) in the carotid arteries of the mice. Results Choline treatment significantly increased plasma TMAO levels in all the groups. Choline treated Nlrp3+/+ mice showed significant impairment in endothelial function and had increased vascular hyper-permeability, enhanced Nlrp3 activation and decreased expression of tight junction proteins like ZO2, VE-cadherin and occludin expression in carotid arteries compared to choline treated Nlrp3−/− mice. Caspase-1 activity and IL-1β production was significantly enhanced in choline treated Nlrp3+/+ mice but not in Nlrp3−/- mice. Real time PCR analysis showed that TLR-4 and inflammatory markers (ICAM & VCAM) were significantly increased in carotid arteries of choline treated Nlrp3+/+ mice compared to Nlrp3−/− mice. Conclusions Our results suggest that chronic choline treatment induced endothelial dysfunction via activation of Nlrp3 inflammasome and other inflammatory markers. Funding Sources NIH - NHLBI, AHA.

scholarly journals Dietary l-Tryptophan Supplementation Enhances the Intestinal Mucosal Barrier Function in Weaned Piglets: Implication of Tryptophan-Metabolizing Microbiota

2018 ◽  
Vol 20 (1) ◽  
pp. 20 ◽  
Author(s):  
Haiwei Liang ◽  
Zhaolai Dai ◽  
Jiao Kou ◽  
Kaiji Sun ◽  
Jingqing Chen ◽  
...  
Keyword(s):  
Tight Junction ◽  
Mucosal Barrier ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tight Junction Proteins ◽  
Weaned Piglets ◽  
Intestinal Mucosal Barrier ◽  
Mucosal Barrier Function ◽  
Small Intestinal ◽  
Junction Proteins

l-Tryptophan (Trp) is known to play an important role in the health of the large intestine. However, a role of dietary Trp in the small-intestinal mucosal barrier and microbiota remains poorly understood. The present study was conducted with weaned piglets to address this issue. Postweaning piglets were fed for 4 weeks a corn- and soybean meal-based diet supplemented with 0 (Control), 0.1, 0.2, or 0.4% Trp. The small-intestinal microbiota and serum amino acids were analyzed by bacterial 16S rRNA gene-based high-throughput sequencing methods and high-performance liquid chromatography, respectively. The mRNA levels for genes involved in host defense and the abundances of tight-junction proteins in jejunum and duodenum were measured by real time-PCR and Western blot techniques, respectively. The concentrations of Trp in the serum of Trp-supplemented piglets increased in a dose-dependent manner. Compared with the control group, dietary supplementation with 0.2–0.4% Trp reduced the abundances of Clostridium sensu stricto and Streptococcus in the jejunum, increased the abundances of Lactobacillus and Clostridium XI (two species of bacteria that can metabolize Trp) in the jejunum, and augmented the concentrations of secretory immunoglobulin A (sIgA) as well as mRNA levels for porcine β-defensins 2 and 3 in jejunal tissues. Moreover, dietary Trp supplementation activated the mammalian target of rapamycin signaling and increased the abundances of tight-junction proteins (zonula occludens (ZO)-1, ZO-3, and claudin-1) in jejunum and duodenum. We suggested that Trp-metabolizing bacteria in the small intestine of weaned pigs primarily mediated the beneficial effects of dietary Trp on its mucosal integrity, health, and function.

scholarly journals Probiotic Mixture Protects Dextran Sulfate Sodium-Induced Colitis by Altering Tight Junction Protein Expressions and Increasing Tregs

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yingdi Zhang ◽  
Xiaojing Zhao ◽  
Yunjuan Zhu ◽  
Jingjing Ma ◽  
Haiqin Ma ◽  
...  
Keyword(s):  
Tight Junction ◽  
Peripheral Blood ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Protective Effects ◽  
Junction Protein

Bifico is a probiotic mixture containing Bifidobacterium, Lactobacillus acidophilus, and Enterococcus. Studies support that Bifico has a protective effect in experimental colitis (IL-10-deficient and TNBS) models and in patients with inflammatory bowel disease (IBD). However, the mechanism underlying the protective effects of this mixture of probiotic bacteria remains incompletely clear. Here, we investigated the effect of Bifico on intestinal inflammation. In an in vivo experiment, dextran sulfate sodium was used to induce colitis. Bifico treatment significantly attenuated the severity of colitis in this model. Bifico increased the expression of tight junction proteins (TJs). In addition, Bifico increased the number of Tregs, but reduced the number of total CD4+ T cells in the peripheral blood. Furthermore, the expression of colonic CD4 protein was decreased while the level of forkhead box P3 (Foxp3) was upregulated. These results suggested that Bifico exerts beneficial effects on experimental colitis by increasing the expressions of TJs, upregulating the number of Tregs, and reducing the total CD4+ T cell number in both colon and peripheral blood. The intestinal damage in the pretreated + treated-Bifico-colitis group was more severe than that in only the pretreated-Bifico-colitis group. This suggested that Bifico might aggravate intestinal damage when the mucosal barrier is impaired.

scholarly journals Role of Tricellular Tight Junction Protein Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Cancer Cells

2019 ◽  
Vol 20 (14) ◽  
pp. 3555 ◽  
Author(s):  
Takayuki Kohno ◽  
Takumi Konno ◽  
Takashi Kojima
Keyword(s):  
Tight Junction ◽  
Cancer Progression ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Endometrial Cells ◽  
Functional Changes ◽  
Junction Protein ◽  
Junction Proteins

Maintaining a robust epithelial barrier requires the accumulation of tight junction proteins, LSR/angulin-1 and tricellulin, at the tricellular contacts. Alterations in the localization of these proteins temporarily cause epithelial barrier dysfunction, which is closely associated with not only physiological differentiation but also cancer progression and metastasis. In normal human endometrial tissues, the endometrial cells undergo repeated proliferation and differentiation under physiological conditions. Recent observations have revealed that the localization and expression of LSR/angulin-1 and tricellulin are altered in a menstrual cycle-dependent manner. Moreover, it has been shown that endometrial cancer progression affects these alterations. This review highlights the differences in the localization and expression of tight junction proteins in normal endometrial cells and endometrial cancers and how they cause functional changes in cells.

Faecal Proteases from Pouchitis Patients Activate Protease Activating Receptor-2 to Disrupt the Epithelial Barrier

2019 ◽  
Vol 13 (12) ◽  
pp. 1558-1568 ◽  
Author(s):  
Sarit Hoffman ◽  
Nathaniel Aviv Cohen ◽  
Ian M Carroll ◽  
Hagit Tulchinsky ◽  
Ilya Borovok ◽  
...  
Keyword(s):  
Tight Junction ◽  
Proteolytic Activity ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Epithelial Permeability ◽  
Tight Junction Proteins ◽  
Microbial Composition ◽  
Junction Protein ◽  
Activating Receptor ◽  
Junction Proteins

Abstract Background and Aims The pathogenesis of pouch inflammation may involve epithelial barrier disruption. We investigated whether faecal proteolytic activity is increased during pouchitis and results in epithelial barrier dysfunction through protease activating receptor [PAR] activation, and assessed whether the intestinal microbiome may be the source of the proteases. Methods Faecal samples were measured for protease activity using a fluorescein isothiocyanate [FITC]-casein florescence assay. Caco-2 cell monolayers were exposed to faecal supernatants to assess permeability to FITC-dextran. Tight junction protein integrity and PAR activation were assessed by immunoblot and immunofluorescence. A truncated PAR2 protein in Caco-2 cells was achieved by stable transfection using CRISPR/Cas9 plasmid. PAR2 activation in pouch biopsies was examined using antibodies directed to the N-terminus of the protein. Microbial composition was analysed based on 16S rRNA gene sequence analysis. Results Ten pouchitis patients, six normal pouch [NP] patients and nine healthy controls [HC] were recruited. The pouchitis patients exhibited a 5.19- and 5.35-fold higher faecal protease [FP] activity [p ≤ 0.05] compared to the NP and HC participants, respectively. The genus Haemophilus was positively associated with FP activity [R = 0.718, false discovery rate < 0.1]. Faecal supernatants from pouchitis patients activated PAR2 on Caco-2 monolayers, disrupted tight junction proteins and increased epithelial permeability. PAR2 truncation in Caco-2 abrogated faecal protease-mediated permeability. Pouch biopsies obtained from pouchitis patients, but not from NP patients, displayed PAR2 activation. Conclusions Protease-producing bacteria may increase faecal proteolytic activity that results in pouch inflammation through disruption of tight junction proteins and increased epithelial permeability in a PAR2-dependent manner. This mechanism may initiate or propagate pouch inflammation.

Protective effects of Notoginsenoside R1 on intestinal ischemia-reperfusion injury in rats

2014 ◽  
Vol 306 (2) ◽  
pp. G111-G122 ◽  
Author(s):  
Chong Li ◽  
Quan Li ◽  
Yu-Ying Liu ◽  
Ming-Xia Wang ◽  
Chun-Shui Pan ◽  
...  
Keyword(s):  
Tight Junction ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Problem ◽  
Protective Effects ◽  
Tight Junction Proteins ◽  
Sprague Dawley ◽  
Component Form ◽  
Junction Proteins

Intestinal ischemia and reperfusion (I/R) is a clinical problem occurred for diverse causes with high mortality. Prophylaxis and treatment of intestinal I/R remains a challenge for clinicians. The purpose of the present study was to explore the role of Notoginsenoside R1 (R1), a major component form of Panax notoginseng, in management of intestinal I/R injury. Intestinal I/R was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 90 min followed by reperfusion for 60 min or 3 days. R1 (10 mg·kg−1·h−1) was administered either 20 min before ischemia or 20 min after reperfusion. Intestinal microcirculation was evaluated by intravital microscopy over 60 min reperfusion. Sixty minutes or 3 days after reperfusion, rats were killed for histological examination of the jejunum tissue and immunohistochemical localization of myeloperoxidase and CD68. ATP, ADP, and AMP content in jejunum tissue was assessed by ELISA. Activation of nuclear factor-κB (NF-κB) and expression of ATP5D and tight junction proteins were determined by Western blotting. The results demonstrated that R1 is capable of attenuating intestinal I/R-induced microvascular hyperpermeability, inflammatory cytokine production, NF-κB activation, and loss of tight junction proteins, as well as improving energy metabolism during I/R. The results of the present study suggest R1 as an option in protecting against intestinal I/R injury.

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