Decarbromodiphenyl ether (BDE-209) promotes monocyte–endothelial adhesion in cultured human aortic endothelial cells through upregulating intercellular adhesion molecule-1

Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 μU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with Nω-nitro-l-arginine, a NOS inhibitor. Nω-Nitro-l-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.

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Insulin Inhibits NFκB and MCP-1 Expression in Human Aortic Endothelial Cells

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.1.7278 ◽

2001 ◽

Vol 86 (1) ◽

pp. 450-453 ◽

Cited By ~ 6

Author(s):

Ahmad Aljada ◽

Husam Ghanim ◽

Rana Saadeh ◽

Paresh Dandona

Keyword(s):

Endothelial Cells ◽

Nuclear Factor Κb ◽

Inhibitory Effect ◽

Binding Activity ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Monocyte Chemoattractant Protein 1 ◽

Aortic Endothelial Cells ◽

Human Aortic Endothelial Cells ◽

Aortic Endothelial

In view of our recent demonstration that insulin inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expression is known to be modulated by nuclear factor-κB (NFκB), we have now investigated whether insulin inhibits intranuclear NFκB binding activity. We have also investigated whether insulin inhibits the pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the inflamed sites and is also regulated by NFκB. Insulin was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000μ U/mL. Intranuclear NFκB binding activity was suppressed by approximately 45% at 100 μU/mL and by 60% at 1000 μU/mL (p< 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100μ U/mL and by 79% at 1000 μU/mL (p < 0.05). We conclude that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal pro-inflammatory transcription factor NFκB and the pro-inflammatory chemokine MCP-1; these effects suggest an anti-inflammatory and potential anti-atherogenic effects of insulin.

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HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

International Journal of Molecular Sciences ◽

10.3390/ijms19113394 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3394 ◽

Cited By ~ 6

Author(s):

Mónica Muñoz-Vega ◽

Felipe Massó ◽

Araceli Páez ◽

Gilberto Vargas-Alarcón ◽

Ramón Coral-Vázquez ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Hdl Cholesterol ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

High Density Lipoproteins ◽

Type I ◽

Intercellular Adhesion Molecule 1 ◽

Apo Ai

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.

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