scholarly journals Microcystins Induces Vascular Inflammation in Human Umbilical Vein Endothelial Cells via Activation of NF-κB

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Shi ◽  
Jie Zhou ◽  
Min Zhang
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Health Hazard ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Microcystins (MCs) produced by toxic cyanobacteria cause serious water pollution and public health hazard to humans and animals. However, direct molecular mechanisms of MC-LR in vascular endothelial cells (ECs) have not been understood yet. In this study, we investigated whether MC-LR induces vascular inflammatory process in cultured human umbilical vein endothelial cells (HUVECs). Our data demonstrated that MC-LR decreased HUVECs proliferation and tube formation and enhanced apoptosis. MC-LR also induced intracellular reactive oxygen species formation (ROS) in HUVECs. The MC-LR directly stimulated phosphorylation of NF-κB. Furthermore, MC-LR also increased cell adhesion molecules (ICAM-1 and VCAM-1) expression in HUVECs. Taken together, the present data suggested that MC-LR induced vascular inflammatory process, which may be closely related to the oxidative stress, NF-κB activation, and cell adhesion molecules expression in HUVECs. Our findings may highlight that MC-LR causes potential damage to blood vessels.

Effect of cytokines on adhesion molecules expression in cell culture of blood vessel endothelium

2002 ◽  
Vol 21 (1) ◽  
pp. 39-40
Author(s):  
Snezana Markovic ◽  
Heide Daxecker ◽  
Markus Raab ◽  
Andrea Griesmacher ◽  
Mathias Müller
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Umbilical Vein ◽  
Surface Expression ◽  
Cd 34 ◽  
Inflammatory Processes ◽  
Umbilical Vein Endothelial Cells ◽  
Stimulation Of

The interaction between leukocytes and endothelial cells plays the essential role in inflammation. Endothelial cells express a variety of adhesive receptors that regulate their adhesion to leukocytes and also to the extracellular matrix. These interactions are complex phenomena that require multiple recognition mechanisms, and include the first rolling and later the stationary adhesion and transmigration of leukocytes. It is known that cytokines have regulatory effects on cell adhesion molecules expression. In the present study we investigated the influence of cytokines (IL-1b, IL-2, IL-4, IL-6, IL-8 IL-10, TNF-a, IFN-g) and the combined use of IL-2, IL-4, IL-6, IL-8 and IL-10 with IL-1b, TNF-b or IFN-g on the expression of adhesion molecules of cultured human umbilical vein endothelial cells (HUVECs) after stimulation for 16 hours. Likewise, in vitro model described herein is designed to mimic the activation of endothelial cells by cytokines as seen during inflammatory processes. This process is mediated by specific cell adhesion molecules being crucial for the generation of immune and inflammatory responses. Therefore, HUVECs are treated with two different cytokine combinations consisting of either IL-2, IL-6, IL-8 IFN-g and TNF-a or IL-1b, IL-2, IL-4, IL-6, IL-10, IFN-g and TNF-a. Endothelial cells were collected from hunam umbilical vain using collagense type II, and cell cultures in complete medium were kept in the incubator (37.4?C, 5% CO2). After stimulation cells were prepared for analysis using tripsinisation procedure. The surface expression of the following adhesion molecules was determined in cultured human umbilical vein endothelial cells (HUVECs) by means of flow-cytometric analysis: CD 62P (P-selectin), CD 62E (E-selectin, ELAM-1) CD 106CD 34 (L-selectin ligand). The highest CD 62E expression on the surface of HUVECs was found when endothelial cells were stimulated with TNF-a alone. Also they were increased after stimulation with IL-1b, while IL-4 led to down-regulation of CD 62E. Incubation of HUVEC monolayers with IL-1b, IL-4 as well as TNF-a and IFN-g, statistically significant, reduced the surface expression of CD 34 while other cytokines did not affect CD 34 expression. Incubation of HUVECs with a single cytokine caused no statistically significant changes in CD 62P expression compared to controls. The most potent effect on CD 54 expression was found under TNF-a stimulation; IL-1b and IFN-g had also amplifying effects, while all other tested cytokines caused no significant changes in surface molecule expression. Surface expression of CD 106 was amplified during incubation with IL-1b, IL-4, TNF-a and IFN-g. Single stimulation of tested cytokines did not significantly alter the cell surface expression of CD 31. Concomitant stimulation with IL-2, IL-4, IL-6, IL-8 or IL-10 with IL-1b, TNF-a or IFN-g led to different effects compared with effects of single cytokine stimulation: CD 62E were up-regulated under co-stimulation with combination of IL-1b and IFN-g, IL-6 and IL-1b, and also in all combinations with TNF-a. Statistically significant differences were found in CD 62P surface expression after concomitant stimulation with IL-1b and IFN-g, and in combinations with TNF-a. Co-stimulation with IL-10 and IL- 1b, TNF-a or IFN-g, or IL-8 with IL-1b or IFNg, IL-6 with IFN-g, IL-4 with TNF-a or IFN-g and IL-2 with IFN-g significantly decreased the level of CD 34 surface expression. (VCAM-1), CD 54 (ICAM-1), CD 31 (PECAM-1) and CD 54 expression was up-regulated after stimulation with IL-1b and IFN-g, and under concomitant stumulation with TNF-a. Surface expression of molecule CD 106 was higher after co-stimulation of cytokines with TNF-a, and IL-4 or IL-10 with IL-1b. These effects indicate modulation of single cytokine effects. Intracellular mechanisms included in those effects need to be investigated. Also there were found modulatory effects of cytokine combinations. Some effects of cytokine combinations were different in comparison to single cytokine effect. This finding indicates that intracellular mechanisms are present and responsible for signal modulation of single cytokine. The application of these two cytokine combinations mimicing inflammation reactions results in effects of comparable dimensions significantly increasing the mean fluorescence intensity of E-selectin, VCAM-1 and ICAM-1 surface expression accompanied by the induction of P-selectin expression. The experiments reveal a strong up-regulation of these cell surface antigens under conditions mimicing inflammation. This is an essential finding stressing the importance of endothelial cells during inflammatory processes.

scholarly journals Hypoxic human umbilical vein endothelial cells induce activation of adherent polymorphonuclear leukocytes

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3705-3716 ◽  
Author(s):  
T Arnould ◽  
C Michiels ◽  
J Remacle
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Superoxide Anion ◽  
Calcium Concentration ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Superoxide Anion Production ◽  
Elastase Inhibitor ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Abstract Several pieces of evidence are reported for the accumulation of activated neutrophils in ischemic and reperfused tissues leading to the transformation of the ischemic tissue into an inflammatory territory and to an enhancement of tissue damages during reoxygenation. However, the molecular mechanisms responsible for these observations and the precise role played by endothelial cells in this process are still poorly understood. In this study, an in vitro model that mimics this situation was used to investigate the effects of hypoxia-incubated human umbilical vein endothelial cells (HUVEC) on polymorphonuclear leukocyte (PMN) functions. A strong PMN activation characterized by an increase in intracellular calcium concentration as well as by superoxide anion release and leukotriene B4 production was observed when these cells were coincubated with hypoxic HUVEC. On the other hand, conditioned medium from hypoxia-incubated HUVEC failed to activate PMN, as determined by the lack of PMN calcium concentration increase, the failure of superoxide anion production enhancement, as well as the absence of effects on the integrin CD18, CD11a, and CD11b expression. These results indicate that the presence of hypoxia- incubated HUVEC is necessary to obtain an activation of the PMN, probably via the adherence process. Once activated by coincubation with hypoxic HUVEC, PMN became cytotoxic, as evidenced by 51Cr released from prelabeled HUVEC. This cytotoxic effect of activated PMN for hypoxic endothelial cells could be prevented by a combination of superoxide dismutase and catalase (94% inhibition), whereas superoxide dismutase alone was inefficient. Antiprotease (alpha 2-macroglobulin) and a specific elastase inhibitor (MAAPV-CMK) were also inefficient. These results correlate very well with the fact that no increase in elastase release could be observed in supernatants from PMN coincubated with hypoxic HUVEC. Furthermore, when adherence process was blocked by oleic acid or by anti-ICAM-1 monoclonal antibodies, protection was, respectively, 90% and 72%. We thus evidenced that free radicals but not elastase released from activated PMN coincubated with hypoxic HUVEC are involved in HUVEC injury. We conclude from these results that PMN activation is initiated by PMN adherence to hypoxic HUVEC. These observations indicate that hypoxic HUVEC may be partly responsible for neutrophil activation observed in ischemic tissues, which is part of the amplification process of tissue damage.

scholarly journals Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells

2019 ◽  
Author(s):  
Jie Qi ◽  
Qichao Wu ◽  
Xuqin Zhu ◽  
Shan Zhang ◽  
Xiangyuan Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nmda Receptor ◽  
Adhesion Molecules ◽  
Umbilical Vein ◽  
Tumor Cell Adhesion ◽  
Human Umbilical Vein ◽  
Akt Phosphorylation ◽  
Dependent Protein ◽  
Umbilical Vein Endothelial Cells

Abstract Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to inhibit tumor metastasis in vitro. Human umbilical vein endothelial cells (HUVECs) cultured in Dulbecco’s modified Eagle’s medium were treated with tumor conditioned medium for 24 h, followed by 4 h of treatment with or without 25 μM of propofol, 10 μM of KN93, 500 μM of MK801, or 20 μM of rapastinel. It was found that propofol inhibited TEC adhesion and the glycolysis level of TECs. Consistently, propofol inhibited the expressions of adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and glycolysis proteins (GLUT1, HK2, and LDHA) in TECs. Moreover, propofol attenuated the expression of HIF-1α, the phosphorylation of AKT and Ca2+/calmodulin-dependent protein kinase II (CaMKII), and the Ca2+ concentration in TECs. MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMKII, both inhibited the expressions of adhesion molecules and glycolysis proteins, in a manner similar to propofol. Additionally, rapastine, an activator of NMDA receptor, could counteract the effects of propofol. Our results indicated that propofol attenuates intracellular Ca2+ concentration, CaMKII and AKT phosphorylation, and HIF-1α expression, probably via inhibiting the NMDA receptor, thus inhibiting glycolysis and adhesion of tumor and endothelial cells.

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