scholarly journals Sodium nitroprusside protects HFD induced gut dysfunction via activating AMPKα/SIRT1 signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaomei Li ◽  
Chen Li ◽  
Yuanqi Li ◽  
Cong Liu ◽  
Xue Liang ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
No Donor ◽  
Cell Monolayers ◽  
Gut Dysfunction ◽  
Epithelial Barrier Dysfunction ◽  
Gut Damage ◽  
Gut Microbiota Dysbiosis ◽  
Junction Proteins

Abstract Background Activation of Adenosine 5′-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism. Methods SNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated. Results SNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling. Conclusions The results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway.

scholarly journals Rebeccamycin Attenuates TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Inhibiting Myosin Light Chain Kinase Production

2017 ◽  
Vol 41 (5) ◽  
pp. 1924-1934 ◽  
Author(s):  
Akihiro Watari ◽  
Yuta Sakamoto ◽  
Kota Hisaie ◽  
Kazuki Iwamoto ◽  
Miho Fueta ◽  
...  
Keyword(s):  
Barrier Function ◽  
Myosin Light Chain ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Cell Monolayers ◽  
Tnf Α ◽  
Epithelial Barrier Dysfunction

Background/Aims: Although proinflammatory cytokine–induced disruption of intestinal epithelial barrier integrity is associated with intestinal inflammatory disease, effective treatment for barrier dysfunction is lacking. Previously, we demonstrated that rebeccamycin alleviates epithelial barrier dysfunction induced by inflammatory cytokines in Caco-2 cell monolayers; however, the underlying mechanism remained unclear. Here, we investigated the mechanism by which rebeccamycin protects the epithelial barrier function of Caco-2 cells exposed to TNF-α. Methods: To confirm the epithelial barrier function of Caco-2 cell monolayers, transepithelial electrical resistance (TER) and paracellular permeability were measured. Production levels and localization of tight junction (TJ) proteins were analyzed by immunoblot and immunofluorescence, respectively. Phosphorylated myosin light chain (pMLC) and MLC kinase (MLCK) mRNA expression levels were determined by immunoblot and quantitative RT-PCR, respectively. Results: Rebeccamycin attenuated the TNF-α-induced reduction in TER and increase in paracellular permeability. Rebeccamycin increased claudin-5 expression, but not claudin-1, -2, -4, occludin or ZO-1 expression, and prevented the TNF-α-induced changes in ZO-1 and occludin localization. Rebeccamycin suppressed the TNF-α-induced increase in MLCK mRNA expression, thus suppressing MLC phosphorylation. The rebeccamycin-mediated reduction in MLCK production and protection of epithelial barrier function were alleviated by Chk1 inhibition. Conclusion: Rebeccamycin attenuates TNF-α-induced disruption of intestinal epithelial barrier integrity by inducing claudin-5 expression and suppressing MLCK production via Chk1 activation.

Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions

2017 ◽  
Vol 8 (3) ◽  
pp. 1144-1151 ◽  
Author(s):  
Qianru Chen ◽  
Oliver Chen ◽  
Isabela M. Martins ◽  
Hu Hou ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Cell Monolayers ◽  
Collagen Peptides ◽  
Epithelial Barrier Dysfunction

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.

scholarly journals The microbiome’s relationship with congenital heart disease: more than a gut feeling

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Dan Feng ◽  
Jason T. Christensen ◽  
Anji T. Yetman ◽  
Merry L. Lindsey ◽  
Amar B. Singh ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Patient Population ◽  
Congenital Heart ◽  
Basic Research ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Dysbiosis ◽  
Epithelial Barrier Dysfunction

AbstractPatients with congenital heart disease (CHD) are at risk for developing intestinal dysbiosis and intestinal epithelial barrier dysfunction due to abnormal gut perfusion or hypoxemia in the context of low cardiac output or cyanosis. Intestinal dysbiosis may contribute to systemic inflammation thereby worsening clinical outcomes in this patient population. Despite significant advances in the management and survival of patients with CHD, morbidity remains significant and questions have arisen as to the role of the microbiome in the inflammatory process. Intestinal dysbiosis and barrier dysfunction experienced in this patient population are increasingly implicated in critical illness. This review highlights possible CHD-microbiome interactions, illustrates underlying signaling mechanisms, and discusses future directions and therapeutic translation of the basic research.

scholarly journals Intestinal Epithelial Barrier Dysfunction in Food Hypersensitivity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Linda Chia-Hui Yu
Keyword(s):  
Mast Cell ◽  
Cell Surface ◽  
Critical Role ◽  
Mast Cell Activation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Food Antigens ◽  
Epithelial Barrier Dysfunction

Intestinal epithelial barrier plays a critical role in the maintenance of gut homeostasis by limiting the penetration of luminal bacteria and dietary allergens, yet allowing antigen sampling for the generation of tolerance. Undigested proteins normally do not gain access to the lamina propria due to physical exclusion by tight junctions at the cell-cell contact sites and intracellular degradation by lysosomal enzymes in enterocytes. An intriguing question then arises: how do macromolecular food antigens cross the epithelial barrier? This review discusses the epithelial barrier dysfunction in sensitized intestine with special emphasis on the molecular mechanism of the enhanced transcytotic rates of allergens. The sensitization phase of allergy is characterized by antigen-induced cross-linking of IgE bound to high affinity FcεRI on mast cell surface, leading to anaphylactic responses. Recent studies have demonstrated that prior to mast cell activation, food allergens are transported in large quantity across the epithelium and are protected from lysosomal degradation by binding to cell surface IgE and low-affinity receptor CD23/FcεRII. Improved immunotherapies are currently under study including anti-IgE and anti-CD23 antibodies for the management of atopic disorders.

scholarly journals Homocysteine Aggravates Intestinal Epithelial Barrier Dysfunction in Rats with Experimental Uremia

2018 ◽  
Vol 43 (5) ◽  
pp. 1516-1528 ◽  
Author(s):  
Shanshan Liang ◽  
Sixiu Liu ◽  
Hua Liu ◽  
Xin He ◽  
Lingshuang Sun ◽  
...  
Keyword(s):  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Dysfunction

scholarly journals Bacteroides fragilis defense against Cronobacter sakazakii-induced pathogenicity by regulating the intestinal epithelial barrier function and attenuating both apoptotic and pyroptotic cell death

2018 ◽  
Author(s):  
Hongying Fan ◽  
Ruqin Lin ◽  
Zhenhui Chen ◽  
Xingyu Leng ◽  
Xianbo Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Necrotizing Enterocolitis ◽  
Neonatal Rat ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Cronobacter Sakazakii ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Dysfunction

AbstractCronobacter sakazakii (CS), an important pathogen, is associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of CS infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was a cross-talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, which revealed that ZY-312 inhibited CS invasion, CS-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. ZY-312 also decreased the expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities, and decreased the relative abundances of Proteobacteria, Gamma proteobacteria, but increased the relative abundance of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic, B. fragilis ZY-312, suppresses CS-induced NEC by modulating the pro-inflammatory response and dual cell death (apoptosis and pyroptosis).Author summaryCronobacter sakazakii, a major necrotizing enterocolitis pathogen, is used as a model microorganism for the study of opportunistic bacteria in the pathogenesis of necrotizing enterocolitis. Here, we have now unequivocally demonstrated that both apoptotic and pyroptotic stimuli contribute to the pathogenesis of Cronobacter sakazakii -induced necrotizing enterocolitis. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. We found that the ZY-312 defense against Cronobacter sakazakii-induced necrotizing enterocolitis by inhibiting Cronobacter sakazakii invasion, epithelial barrier dysfunction, the expression of inflammatory cytokines and dual cell death (pyroptosis and apoptosis). This study demonstrates the utility of ZY-312 as a promising probiotic agent for the prevention and treatment of various intestinal diseases, including NEC.

scholarly journals Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

2013 ◽  
Vol 304 (5) ◽  
pp. G479-G489 ◽  
Author(s):  
Katherine R. Groschwitz ◽  
David Wu ◽  
Heather Osterfeld ◽  
Richard Ahrens ◽  
Simon P. Hogan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction

Mast cells regulate intestinal barrier function during disease and homeostasis. Secretion of the mast cell-specific serine protease chymase regulates homeostasis. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial (Caco-2 BBe) cell monolayers induced a significant reduction in transepithelial resistance, indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Consistent with this observation, in vitro analysis revealed chymase-induced PAR-2 activation and increased MAPK activity and MMP-2 expression. Pharmacological and small interfering RNA-mediated antagonism of PAR-2 and MMP-2 significantly attenuated chymase-stimulated barrier dysfunction. Additionally, the chymase/MMP-2-mediated intestinal epithelial dysfunction was associated with a significant reduction in the tight junction protein claudin-5, which was partially restored by MMP-2 inhibition. Finally, incubation of Caco-2 BBe cells with chymase-sufficient, but not chymase-deficient, bone marrow-derived mast cells decreased barrier function, which was attenuated by the chymase inhibitor chymostatin. Collectively, these results suggest that mast cell/chymase-mediated intestinal epithelial barrier function is mediated by PAR-2/MMP-2-dependent pathways.

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