Proinflammatory factors present in sera from patients with acute dengue infection induce activation and apoptosis of human microvascular endothelial cells: Possible role of TNF-α in endothelial cell damage in dengue

Cytokine ◽  
2005 ◽  
Vol 30 (6) ◽  
pp. 359-365 ◽  
Author(s):  
José E. Cardier ◽  
Eliana Mariño ◽  
Egidio Romano ◽  
Peter Taylor ◽  
Ferdinando Liprandi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Damage ◽  
Dengue Infection ◽  
Microvascular Endothelial Cells ◽  
Endothelial Cell Damage ◽  
Tnf Α ◽  
Microvascular Endothelial ◽  
Proinflammatory Factors

scholarly journals Vitamin D ameliorated endothelial cell damage induced by diabetes via regulation of lncRNA MEG3 in human umbilical vein endothelial cells

2020 ◽  
Author(s):  
Hua Wei ◽  
Qiongfang Zhang ◽  
Jun Li ◽  
Jing Yang ◽  
Bin Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Damage ◽  
Umbilical Vein ◽  
Nuclear Volume ◽  
Endothelial Cell Damage ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Umbilical Vein Endothelial Cells

IntroductionThe purpose of this study was to investigate long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) effects in vitamin D (Vit. D) treatment in endothelial cell damage induced by diabetes.Material and methodsWe used human umbilical vein endothelial cells (HUVECs) as a research objective in our study and used high glucose in a diabetic cell model. We evaluated cell apoptosis by flow cytometry, inflammatory factors (IL-6, IL-1β and TNF-α) concentrations by ELISA assay, relative gene and protein expression by RT-qPCR and WB assay, and NF-κB(p65) nuclear volume by cellular immunofluorescence.ResultsCompared with the NC (normal control) group, the cell apoptosis rate was significantly increased, inflammatory factor (IL-6, IL-1β and TNF-α) concentrations were significantly up-regulated, lncRNA MEG3 gene expression was significantly depressed, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor B p65 (NF-κB(p65)) gene and protein expression levels were significantly increased and NF-κB(p65) nuclear volume was significantly up-regulated (p < 0.001, respectively). With Vit. D supplementation, compared with the Model group, Vit. D improved endothelial cell damage induced by diabetes, while lncRNA MEG3 was significantly increased and the TLR4/MyD88/NF-κB(p65) pathway was significantly depressed dose-dependently (all p < 0.05). With sh-MEG3 transfection, the Vit. D treatment effects were significantly reduced.ConclusionsVit. D improved endothelial cell damage induced by diabetes via lncRNA MEG3 up-regulation in vitro study.

scholarly journals Verocytotoxin-Induced Apoptosis of Human Microvascular Endothelial Cells

2001 ◽  
Vol 12 (4) ◽  
pp. 767-778
Author(s):  
ANTONETTA H. J. M. PIJPERS ◽  
PETRA A. VAN SETTEN ◽  
LAMBERTUS P. W. J. VAN DEN HEUVEL ◽  
KAREL J. M. ASSMANN ◽  
HENDRIKUS B. P. M. DIJKMAN ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Protein Synthesis ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Microvascular Endothelial Cells ◽  
Tnf Α ◽  
Microvascular Endothelial ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Abstract. The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-α (TNF-α). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-α interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-α-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

scholarly journals Glutathione Peroxidase-1 Deficiency Augments Proinflammatory Cytokine-induced Redox Signaling and Human Endothelial Cell Activation

2011 ◽  
Vol 286 (41) ◽  
pp. 35407-35417 ◽  
Author(s):  
Edith Lubos ◽  
Neil J. Kelly ◽  
Scott R. Oldebeken ◽  
Jane A. Leopold ◽  
Ying-Yi Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Glutathione Peroxidase ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Microvascular Endothelial Cells ◽  
Endothelial Cell Activation ◽  
Glutathione Peroxidase 1 ◽  
Tnf Α ◽  
Microvascular Endothelial

Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant enzyme, the deficiency of which promotes atherogenesis. Accordingly, we examined the mechanisms by which GPx-1 deficiency enhances endothelial cell activation and inflammation. In human microvascular endothelial cells, we found that GPx-1 deficiency augments intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression by redox-dependent mechanisms that involve NFκB. Suppression of GPx-1 enhanced TNF-α-induced ROS production and ICAM-1 expression, whereas overexpression of GPx-1 attenuated these TNF-α-mediated responses. GPx-1 deficiency prolonged TNF-α-induced IκBα degradation and activation of ERK1/2 and JNK. JNK or NFκB inhibition attenuated TNF-α induction of ICAM-1 and VCAM-1 expression in GPx-1-deficient and control cells, whereas ERK1/2 inhibition attenuated only VCAM-1 expression. To analyze further signaling pathways involved in GPx-1-mediated protection from TNF-α-induced ROS, we performed microarray analysis of human microvascular endothelial cells treated with TNF-α in the presence and absence of GPx-1. Among the genes whose expression changed significantly, dual specificity phosphatase 4 (DUSP4), encoding an antagonist of MAPK signaling, was down-regulated by GPx-1 suppression. Targeted DUSP4 knockdown enhanced TNF-α-mediated ERK1/2 pathway activation and resulted in increased adhesion molecule expression, indicating that GPx-1 deficiency may augment TNF-α-mediated events, in part, by regulating DUSP4.

Inflammatory stress increases receptor for lysophosphatidylcholine in human microvascular endothelial cells

2003 ◽  
Vol 285 (4) ◽  
pp. H1786-H1789 ◽  
Author(s):  
Hazel Lum ◽  
Jing Qiao ◽  
Robert J. Walter ◽  
Fei Huang ◽  
Papasani V. Subbaiah ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
G Protein ◽  
Cell Monolayer ◽  
Microvascular Endothelial Cells ◽  
Pcr Analysis ◽  
Binding Studies ◽  
Tnf Α ◽  
Microvascular Endothelial ◽  
G Protein Coupled

The atherogenic serum lysophosphatidylcholine (LPC) is known to mediate vascular endothelial responses ranging from upregulation of adhesion molecules and growth factors to secretion of chemokines and superoxide anion. We investigated whether endothelial cells express receptors for LPC, which may account for their actions. Human brain microvascular (HBMEC) and dermal microvascular endothelial cells (HMEC) were prepared for RT-PCR analysis for possible expression of the G protein-coupled receptors, GPR4 and G2A, which are believed to be specific LPC receptors. Results indicated that HBMEC expressed low basal GPR4 mRNA, but stimulation with tumor necrosis factor-α (TNF-α) (100 U/ml) or H2O2 (50 μmol/l) for 2 h or overnight upregulated expression severalfold. In contrast, HMEC expressed high basal GPR4 mRNA, which was not further increased by either TNF-α or H2O2 stimulation. Another LPC receptor, G2A, was not detected in either endothelial cell type. Competition binding studies were made to evaluate specific binding of [3H]LPC to the intact endothelial cell monolayer. Basal specific [3H]LPC binding in HBMEC was approximately eight times lower than in HMEC; however, TNF-α or H2O2 stimulation increased [3H]LPC binding on HMBEC but not HMEC. The results indicated that GPR4 expression was consistent with specific [3H]LPC binding. Overall, we report that endothelial cells selectively expressed GPR4, a specific LPC receptor. Furthermore, GPR4 expression by HBMEC, but not HMEC, was increased by inflammatory stresses. We conclude that endogenous GPR4 in endothelial cells may be a potential G protein-coupled receptor by which LPC signals proinflammatory activities.

scholarly journals Anti-Inflammatory Effect and Cellular Uptake Mechanism of Carbon Nanodots in in Human Microvascular Endothelial Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1247
Author(s):  
Sarah Belperain ◽  
Zi Yae Kang ◽  
Andrew Dunphy ◽  
Brandon Priebe ◽  
Norman H. L. Chiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Synthesis Method ◽  
Microvascular Endothelial Cells ◽  
Carbon Nanodots ◽  
Uptake Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Microvascular Endothelial

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.

scholarly journals A tumor-promoting role for soluble TβRIII in glioblastoma

2021 ◽  
Author(s):  
Isabel Burghardt ◽  
Judith Johanna Schroeder ◽  
Tobias Weiss ◽  
Dorothee Gramatzki ◽  
Michael Weller
Keyword(s):  
Endothelial Cells ◽  
Ex Vivo ◽  
Microvascular Endothelial Cells ◽  
Smad2 Phosphorylation ◽  
Cell Gene Expression ◽  
Microvascular Endothelial ◽  
Cell Gene ◽  
Mouse Glioma

Abstract Purpose Members of the transforming growth factor (TGF)-β superfamily play a key role in the regulation of the malignant phenotype of glioblastoma by promoting invasiveness, angiogenesis, immunosuppression, and maintaining stem cell-like properties. Betaglycan, a TGF-β coreceptor also known as TGF-β receptor III (TβRIII), interacts with members of the TGF-β superfamily and acts as membrane-associated or shed molecule. Shed, soluble TβRIII (sTβRIII) is produced upon ectodomain cleavage of the membrane-bound form. Elucidating the role of TβRIII may improve our understanding of TGF-β pathway activity in glioblastoma Methods Protein levels of TβRIII were determined by immunohistochemical analyses and ex vivo single-cell gene expression profiling of glioblastoma tissue respectively. In vitro, TβRIII levels were assessed investigating long-term glioma cell lines (LTCs), cultured human brain-derived microvascular endothelial cells (hCMECs), glioblastoma-derived microvascular endothelial cells, and glioma-initiating cell lines (GICs). The impact of TβRIII on TGF-β signaling was investigated, and results were validated in a xenograft mouse glioma model Results Immunohistochemistry and ex vivo single-cell gene expression profiling of glioblastoma tissue showed that TβRIII was expressed in the tumor tissue, predominantly in the vascular compartment. We confirmed this pattern of TβRIII expression in vitro. Specifically, we detected sTβRIII in glioblastoma-derived microvascular endothelial cells. STβRIII facilitated TGF-β-induced Smad2 phosphorylation in vitro and overexpression of sTβRIII in a xenograft mouse glioma model led to increased levels of Smad2 phosphorylation, increased tumor volume, and decreased survival Conclusions These data shed light on the potential tumor-promoting role of extracellular shed TβRIII which may be released by glioblastoma endothelium with high sTβRIII levels.

Isolation and characterization of human and rat cardiac microvascular endothelial cells

1993 ◽  
Vol 264 (2) ◽  
pp. H639-H652 ◽  
Author(s):  
M. Nishida ◽  
W. W. Carley ◽  
M. E. Gerritsen ◽  
O. Ellingsen ◽  
R. A. Kelly ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelium ◽  
Adult Rat ◽  
Isolation And Characterization ◽  
Ventricular Tissue ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

Although reciprocal intercellular signaling may occur between endocardial or microvascular endothelium and cardiac myocytes, suitable in vitro models have not been well characterized. In this report, we describe the isolation and primary culture of cardiac microvascular endothelial cells (CMEC) from both adult rat and human ventricular tissue. Differential uptake of fluorescently labeled acetylated low-density lipoprotein (Ac-LDL) indicated that primary isolates of rat CMEC were quite homogeneous, unlike primary isolates of human ventricular tissue, which required cell sorting based on Ac-LDL uptake to create endothelial cell-enriched primary cultures. The endothelial phenotype of both primary isolates and postsort subcultured CMEC and their microvascular origin were determined by characteristic histochemical staining for a number of endothelial cell-specific markers, by the absence of cells with fibroblast or pericyte-specific cell surface antigens, and by rapid tube formation on purified basement membrane preparations. Importantly, [3H]-thymidine uptake was increased 2.3-fold in subconfluent rat microvascular endothelial cells 3 days after coculture with adult rat ventricular myocytes because of release of an endothelial cell mitogen(s) into the extracellular matrix, resulting in a 68% increase in cell number compared with CMEC in monoculture. Thus biologically relevant cell-to-cell interactions can be modeled with this in vitro system.

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