Search results for: Human Large Intestine Microvascular Endothelial Cells
#30569099 2018/12/18 To Up
Kaempferol inhibits multiple pathways involved in the secretion of inflammatory mediators from LPS‑induced rat intestinal microvascular endothelial cells.Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of the small and/or large intestine. Endothelial expression of inflammatory mediators, including cytokines and adhesion molecules, serves a critical role in the initiation and progression of IBD. The dietary flavonoid, kaempferol, has been reported to inhibit expression of inflammatory mediators; however, the underlying mechanisms require further investigation. In the present study, a novel molecular mechanism of kaempferol against IBD was identified. The potential anti‑inflammatory effect of kaempferol in a cellular model of intestinal inflammation was assessed using lipopolysaccharide (LPS)‑induced rat intestinal microvascular endothelial cells (RIMVECs), and an underlying key molecular mechanism was identified. RIMVECs were pretreated with kaempferol of various concentrations (12.5, 25 and 50 µM) followed by LPS (10 µg/ml) stimulation. ELISA was used to examine the protein levels of tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), IL‑6, intercellular adhesion molecule-1 (ICAM‑1) and vascular cell adhesion molecule-1 (VCAM‑1) in the supernatant. Protein expression levels of Toll‑like receptor 4 (TLR4), nuclear factor‑κB (NF‑κB) p65, inhibitor of NF‑κB, mitogen‑activated protein kinase p38 and signal transducer and activator of transcription (STAT) in cells were measured by western blotting. Kaempferol significantly reduced the overproduction of TNF‑α, IL‑1β, interleukin‑6, ICAM‑1 and VCAM‑1 induced by LPS, indicating the negative regulation of kaempferol in TLR4, NF‑κB and STAT signaling underlying intestinal inflammation. The present results provide support for the potential use of kaempferol as an effective therapeutic agent for IBD treatment.
Yifei Bian, Ping Liu, Jia Zhong, Yusheng Hu, Yingsai Fan, Shen Zhuang, Zhongjie Liu
2384 related Products with: Kaempferol inhibits multiple pathways involved in the secretion of inflammatory mediators from LPS‑induced rat intestinal microvascular endothelial cells.96 assays1.00 flask96 wells1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask
#30510170 2018/12/03 To Up
Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.Clostridium difficile infection (CDI) is mediated by two major exotoxins, toxin A (TcdA) and toxin B (TcdB), that damage the colonic epithelial barrier and induce inflammatory responses. The function of the colonic vascular barrier during CDI has been relatively understudied. Here we report increased colonic vascular permeability in CDI mice and elevated vascular endothelial growth factor A (VEGF-A), which was induced in vivo by infection with TcdA- and/or TcdB-producing C. difficile strains but not with a TcdATcdB isogenic mutant. TcdA or TcdB also induced the expression of VEGF-A in human colonic mucosal biopsies. Hypoxia-inducible factor signalling appeared to mediate toxin-induced VEGF production in colonocytes, which can further stimulate human intestinal microvascular endothelial cells. Both neutralization of VEGF-A and inhibition of its signalling pathway attenuated CDI in vivo. Compared to healthy controls, CDI patients had significantly higher serum VEGF-A that subsequently decreased after treatment. Our findings indicate critical roles for toxin-induced VEGF-A and colonic vascular permeability in CDI pathogenesis and may also point to the pathophysiological significance of the gut vascular barrier in response to virulence factors of enteric pathogens. As an alternative to pathogen-targeted therapy, this study may enable new host-directed therapeutic approaches for severe, refractory CDI.
Jun Huang, Ciarán P Kelly, Kyriaki Bakirtzi, Javier A Villafuerte Gálvez, Dena Lyras, Steven J Mileto, Sarah Larcombe, Hua Xu, Xiaotong Yang, Kelsey S Shields, Weishu Zhu, Yi Zhang, Jeffrey D Goldsmith, Ishan J Patel, Joshua Hansen, Meijin Huang, Seppo Yla-Herttuala, Alan C Moss, Daniel Paredes-Sabja, Charalabos Pothoulakis, Yatrik M Shah, Jianping Wang, Xinhua Chen
2682 related Products with: Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.100 1 mg100 200 ug100 200 ug100 200 ug200 200 ug1 mg
#29214442 2017/12/06 To Up
Shiga toxin triggers endothelial and podocyte injury: the role of complement activation.Shiga toxin (Stx)-producing Escherichia coli (STEC) is the offending agent in post-diarrhea-associated hemolytic uremic syndrome (HUS), a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney failure, with thrombi occluding the renal microvasculature. Endothelial dysfunction has been recognized as the trigger event in the development of microangiopathic processes. Glomerular endothelial cells are susceptible to the toxic effects of Stxs that, via nuclear factor kappa B (NF-κB) activation, induce the expression of genes encoding for adhesion molecules and chemokines, culminating in leukocyte adhesion and platelet thrombus formation on the activated endothelium. Complement activation via the alternative pathway has been seen in patients during the acute phase of STEC-associated HUS. Experimental evidence has highlighted the role of complement proteins in driving glomerular endothelium toward a thrombogenic phenotype. At the glomerular level, podocytes are also an important target of Stx-induced complement activation. Glomerular injury as a consequence of podocyte dysfunction and loss is thus a mechanism that might affect long-term renal outcomes in the disease. New approaches to targeting the complement system may be useful therapeutic options for patients with STEC-HUS.
Carlamaria Zoja, Simona Buelli, Marina Morigi
1888 related Products with: Shiga toxin triggers endothelial and podocyte injury: the role of complement activation.100ug100 ug100 ug100μg1.00 flask50 ug 100.00 ug 6 ml Ready-to-use 100ug
#29185482 2017/11/29 To Up
A novel role for OATP2A1/SLCO2A1 in a murine model of colon cancer.Prostaglandin E (PGE) is associated with proliferation and angiogenesis in colorectal tumours. The role of prostaglandin transporter OATP2A1/SLCO2A1 in colon cancer tumorogenesis is unknown. We evaluated mice of various Slco2a1 genotypes in a murine model of colon cancer, the adenomatous polyposis (APC) mutant (Apc ) model. Median lifespan was significantly extended from 19 weeks in Slco2a1 /Apc mice to 25 weeks in Slco2a1 /Apc mice. Survival was directly related to a reduction in the number of large polyps in the Slco2a1 /Apc compared to the Slco2a1 /Apc or Slco2a1 /Apc mice. The large polyps from the Slco2a1 /Apc mice had significant reductions in microvascular density, consistent with the high expression of Slco2a1 in the tumour-associated vascular endothelial cells. Chemical suppression of OATP2A1 function significantly reduced tube formation and wound-healing activity of PGE in human vascular endothelial cells (HUVECs) although the amount of extracellular PGE was not affected by an OATP2A1 inhibitor. Further an in vivo model of angiogenesis, showed a significant reduction of haemoglobin content (54.2%) in sponges implanted into Slco2a1 , compared to wildtype mice. These studies indicate that OATP2A1 is likely to promote tumorogenesis by PGE uptake into the endothelial cells, suggesting that blockade of OATP2A1 is an additional pharmacologic strategy to improve colon cancer outcomes.
Takeo Nakanishi, Yasuhiro Ohno, Rika Aotani, Shio Maruyama, Hiroaki Shimada, Shunsuke Kamo, Hiroko Oshima, Masanobu Oshima, John D Schuetz, Ikumi Tamai
#28827082 2017/08/04 To Up
MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice.Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation.
Federica Ungaro, Carlotta Tacconi, Luca Massimino, Paola Antonia Corsetto, Carmen Correale, Philippe Fonteyne, Andrea Piontini, Valeria Garzarelli, Francesca Calcaterra, Silvia Della Bella, Antonino Spinelli, Michele Carvello, Angela Maria Rizzo, Stefania Vetrano, Luciana Petti, Gionata Fiorino, Federica Furfaro, Domenico Mavilio, Krishna Rao Maddipati, Alberto Malesci, Laurent Peyrin-Biroulet, Silvia D'Alessio, Silvio Danese
1955 related Products with: MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice.100ug1.00 flask8 Sample Kit 6 ml Ready-to-use 10 mg1000 TESTS/0.65ml1.00 flask 25UG100 mg1.00 flask4 Arrays/Slide
#27981571 2017/01/27 To Up
Haematopoietic prolyl hydroxylase-1 deficiency promotes M2 macrophage polarization and is both necessary and sufficient to protect against experimental colitis.Prolyl hydroxylase domain-containing proteins (PHDs) regulate the adaptation of cells to hypoxia. Pan-hydroxylase inhibition is protective in experimental colitis, in which PHD1 plays a prominent role. However, it is currently unknown how PHD1 targeting regulates this protection and which cell type(s) are involved. Here, we demonstrated that Phd1 deletion in endothelial and haematopoietic cells (Phd1 Tie2:cre) protected mice from dextran sulphate sodium (DSS)-induced colitis, with reduced epithelial erosions, immune cell infiltration, and colonic microvascular dysfunction, whereas the response of Phd2 Tie2:cre and Phd3 Tie2:cre mice to DSS was similar to that of their littermate controls. Using bone marrow chimeras and cell-specific cre mice, we demonstrated that ablation of Phd1 in haematopoietic cells but not in endothelial cells was both necessary and sufficient to inhibit experimental colitis. This effect relied, at least in part, on skewing of Phd1-deficient bone marrow-derived macrophages towards an anti-inflammatory M2 phenotype. These cells showed an attenuated nuclear factor-κB-dependent response to lipopolysaccharide (LPS), which in turn diminished endothelial chemokine expression. In addition, Phd1 deficiency in dendritic cells significantly reduced interleukin-1β production in response to LPS. Taken together, our results further support the development of selective PHD1 inhibitors for ulcerative colitis, and identify haematopoietic cells as their primary target. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sophie Van Welden, Martine De Vos, Ben Wielockx, Simon J Tavernier, Melissa Dullaers, Sara Neyt, Benedicte Descamps, Lindsey Devisscher, Sarah Devriese, Lien Van den Bossche, Tom Holvoet, Ann Baeyens, Carmen Correale, Silvia D'Alessio, Christian Vanhove, Filip De Vos, Bruno Verhasselt, Georg Breier, Bart N Lambrecht, Sophie Janssens, Peter Carmeliet, Silvio Danese, Dirk Elewaut, Debby Laukens, Pieter Hindryckx
2048 related Products with: Haematopoietic prolyl hydroxylase-1 deficiency promotes M2 macrophage polarization and is both necessary and sufficient to protect against experimental colitis.100ug1000 TESTS/0.65ml100ul100ug1000 tests1000 100ug Lyophilized100ul100ug100 mg100ul100ug
#25644809 2015/02/02 To Up
Corosolic Acid Exhibits Anti-angiogenic and Anti-lymphangiogenic Effects on In Vitro Endothelial Cells and on an In Vivo CT-26 Colon Carcinoma Animal Model.We describe the anti-angiogenic and anti-lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT-26 animal model was employed to determine the in vivo anti-angiogenic and anti-lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT-26 cells, mediated by the activation of caspase-3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin-1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti-angiogenic activity that can suppress FAK signaling induced by angiopoietin-1.
Ki Hyun Yoo, Jong-Hwa Park, Dae Young Lee, Jeon Hwang-Bo, Nam In Baek, In Sik Chung
2038 related Products with: Corosolic Acid Exhibits Anti-angiogenic and Anti-lymphangiogenic Effects on In Vitro Endothelial Cells and on an In Vivo CT-26 Colon Carcinoma Animal Model.100ug100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized
#25307345 2014/10/07 To Up
The neurotensin-HIF-1α-VEGFα axis orchestrates hypoxia, colonic inflammation, and intestinal angiogenesis.The expression of neurotensin (NT) and its receptor (NTR1) is up-regulated in experimental colitis and inflammatory bowel disease; NT/NTR1 interactions regulate gut inflammation. During active inflammation, metabolic shifts toward hypoxia lead to the activation of hypoxia-inducible factor (HIF)-1, which enhances vascular endothelial growth factor (VEGF) expression, promoting angiogenesis. We hypothesized that NT/NTR1 signaling regulates intestinal manifestations of hypoxia and angiogenesis by promoting HIF-1 transcriptional activity and VEGFα expression in experimental colitis. We studied NTR1 signaling in colitis-associated angiogenesis using 2,4,6-trinitrobenzenesulfonic acid-treated wild-type and NTR1-knockout mice. The effects of NT on HIF-1α and VEGFα were assessed on human colonic epithelial cells overexpressing NTR1 (NCM460-NTR1) and human intestinal microvascular-endothelial cells. NTR1-knockout mice had reduced microvascular density and mucosal integrity score compared with wild-type mice after 2,4,6-trinitrobenzenesulfonic acid treatment. VEGFα mRNA levels were increased in NCM460-NTR1 cells treated with 10(-7) mol/L NT, at 1 and 6 hours post-treatment. NT exposure in NCM460-NTR1 cells caused stabilization, nuclear translocation, and transcriptional activity of HIF-1α in a diacylglycerol kinase-dependent manner. NT did not stimulate tube formation in isolated human intestinal macrovascular endothelial cells but did so in human intestinal macrovascular endothelial cells cocultured with NCM460-NTR1 cells. Our results demonstrate the importance of an NTR1-HIF-1α-VEGFα axis in intestinal angiogenic responses and in the pathophysiology of colitis and inflammatory bowel disease.
Kyriaki Bakirtzi, Gail West, Claudio Fiocchi, Ivy Ka Man Law, Dimitrios Iliopoulos, Charalabos Pothoulakis
1180 related Products with: The neurotensin-HIF-1α-VEGFα axis orchestrates hypoxia, colonic inflammation, and intestinal angiogenesis.500 Units8 Sample Kit96 wells (1 kit) 100ul100ug1100ug4 Arrays/Slide100ug16-22 Sample Kit1000 TESTS/0.65ml
#24914216 2014/06/09 To Up
Differential effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on chemokine and proinflammatory cytokine expression in human macrophage, colonic epithelial, and brain microvascular endothelial cell lines.Subtilase cytotoxin (SubAB) is the prototype of a recently emerged family of AB5 cytotoxins produced by Shiga-toxigenic Escherichia coli (STEC). Its mechanism of action involves highly specific A-subunit-mediated proteolytic cleavage of the essential endoplasmic reticulum (ER) chaperone BiP. Our previous in vivo studies showed that intraperitoneal injection of purified SubAB causes a major redistribution of leukocytes and elevated leukocyte apoptosis in mice, as well as profound splenic atrophy. In the current study, we investigated selected chemokine and proinflammatory cytokine responses to treatment with SubAB, a nontoxic derivative (SubAA272B), or Shiga toxin 2 (Stx2) in human macrophage (U937), brain microvascular endothelial (HBMEC), and colonic epithelial (HCT-8) cell lines, at the levels of secreted protein, cell-associated protein, and gene expression. Stx2 treatment upregulated expression of chemokines and cytokines at both the protein and mRNA levels. In contrast, SubAB induced significant decreases in secreted interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in all three tested cell lines and a significant decrease in secreted IL-6 in HBMECs. The downregulation of secreted chemokines or cytokines was not observed in SubAA272B-treated cells, indicating a requirement for BiP cleavage. The downregulation of secreted chemokines and cytokines by SubAB was not reflected at the mRNA and cell-associated protein levels, suggesting a SubAB-induced export defect.
Hui Wang, Trisha J Rogers, James C Paton, Adrienne W Paton
1265 related Products with: Differential effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on chemokine and proinflammatory cytokine expression in human macrophage, colonic epithelial, and brain microvascular endothelial cell lines.1.00 flask1.00 flask1.00 flask1 mg10 ug1.00 flask1.00 flask200ul1.00 flask1000 1.00 flask10 mg
#24682411 2014/03/30 To Up
Regulated expression of leukocyte-specific transcript (LST) 1 in human intestinal inflammation.Leukocyte-specific transcript 1 (LST1) encoded peptides are involved in immunomodulation and nanotube-mediated cell-cell communication. The aim of this study was to assess the expression of LST1 in colonic epithelium and endothelium during intestinal inflammation.
Jan Heidemann, Moritz Kebschull, Phil Robin Tepasse, Dominik Bettenworth
1739 related Products with: Regulated expression of leukocyte-specific transcript (LST) 1 in human intestinal inflammation.4 Membranes/Box4 Membranes/Box4 Membranes/Box 100ul100ug Lyophilized4 Arrays/Slide4 Arrays/Slide8 Sample Kit 100ul4 Membranes/Box100ug 100ul
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