Sensitization of Human Aortic Endothelial Cells to Lipopolysaccharide via Regulation of Toll-Like Receptor 4 by Bacterial Fimbria-Dependent Invasion

ABSTRACT Toll-like receptors (TLRs) are differentially up-regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Epidemiological data support the idea that periodontal disease may be a risk factor for acceleration of atherosclerosis. Porphyromonas gingivalis, the etiological agent of periodontal disease, invades endothelium, has been detected in human atheromatous tissue, and accelerates atheroma formation in apolipoprotein E−/− mice with concurrent induction of TLRs in the aorta. As endothelial cells can present antigen via TLRs and play an important role in the development of atherosclerosis, we examined TLR expression in human aortic endothelial cells (HAEC) cultured with wild-type P. gingivalis, a fimbria-deficient mutant, and purified antigens. We observed increased TLR expression in HAEC infected with wild-type P. gingivalis by fluorescence-activated cell sorter, but not with noninvasive, fimbria-deficient mutant or purified P. gingivalis antigens. Following a wild-type P. gingivalis challenge, functional TLR2 and TLR4 activation was assessed by subsequent stimulation with TLR agonists Staphylococcus aureus lipoteichoic acid (SLTA; TLR2 ligand) and Escherichia coli lipopolysaccharide (LPS; TLR4 ligand). Unchallenged HAEC failed to elicit monocyte chemoattractant protein 1 (MCP-1) in response to LPS or SLTA but did so when cultured with wild-type P. gingivalis. P. gingivalis-induced TLR2 and -4 expression on HAEC functionally reacted to SLTA and E. coli LPS as measured by a further increase in MCP-1 production. Furthermore, MCP-1 expression elicited by E. coli LPS was inhibitable with TLR4-specific antibody and polymyxin B. These results indicate that invasive P. gingivalis stimulates TLR expression on the surface of endothelium and these primed cells respond to defined TLR-specific ligands.

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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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Homocysteine Induces Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Aortic Endothelial Cells

Circulation ◽

10.1161/01.cir.103.22.2717 ◽

2001 ◽

Vol 103 (22) ◽

pp. 2717-2723 ◽

Cited By ~ 193

Author(s):

Ranjana Poddar ◽

Natarajan Sivasubramanian ◽

Patricia M. DiBello ◽

Killian Robinson ◽

Donald W. Jacobsen

Keyword(s):

Endothelial Cells ◽

Interleukin 8 ◽

Monocyte Chemoattractant Protein 1 ◽

Aortic Endothelial Cells ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

Human Aortic Endothelial Cells ◽

Aortic Endothelial

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Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316725 ◽

2021 ◽

Author(s):

Srividya Velagapudi ◽

Lucia Rohrer ◽

Francesco Poti ◽

Renate Feuerborn ◽

Damir Perisa ◽

...

Keyword(s):

Endothelial Cells ◽

Peritoneal Cavity ◽

Knockout Mice ◽

Evans Blue ◽

Wild Type ◽

Aortic Endothelial Cells ◽

Transendothelial Transport ◽

Sphingosine 1 Phosphate ◽

Human Aortic Endothelial Cells ◽

Aortic Endothelial

Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P 1 (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells. We also compared the transport of fluorescently-labeled HDL or Evans Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (apoE-haploinsufficient mice with endothelium-specific knockin of S1P 1 ) or without (control mice, ie, apoE-haploinsufficient mice without endothelium-specific knockin of S1P 1 ) endothelium-specific knockin of S1P 1 . The binding, association, and transport of HDL from Apom knockout mice and human apoM-depleted HDL by bovine aortic endothelial cells was significantly lower than that of HDL from wild-type mice and human apoM-containing HDL, respectively. The binding, uptake, and transport of 125 I-HDL by human aortic endothelial cells was increased by an S1P 1 agonist but decreased by an S1P 1 inhibitor. Silencing of SR-BI (scavenger receptor BI) abrogated the stimulation of 125 I-HDL transport by the S1P 1 agonist. Compared with control mice, that is, apoE-haploinsufficient mice without endothelium-specific knockin of S1P 1 , apoE-haploinsufficient mice with endothelium-specific knockin of S1P 1 showed decreased transport of Evans Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. Conclusions: ApoM and S1P 1 promote transendothelial HDL transport. Their opposite effect on transendothelial transport of albumin and HDL indicates that HDL passes endothelial barriers by specific mechanisms rather than passive filtration.

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