Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells

1999 ◽  
Vol 276 (6) ◽  
pp. H2044-H2052 ◽  
Author(s):  
Carsten Willam ◽  
Ralf Schindler ◽  
Ulrich Frei ◽  
Kai-Uwe Eckardt
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
White Blood Cells ◽  
Free Radical Scavengers ◽  
Intercellular Adhesion Molecule ◽  
Induced Expression ◽  
Tnf Α

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte β-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-α (TNF-α). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-α-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-α-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under “normoxic” (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-l-arginine methyl ester (l-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of l-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-l-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.

Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells

1996 ◽  
Vol 270 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
M. G. Bouma ◽  
F. A. van den Wildenberg ◽  
W. A. Buurman
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Cytokine Release ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammatory

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.

scholarly journals A Proteasome Inhibitor, an Antioxidant, or a Salicylate, but not a Glucocorticoid, Blocks Constitutive and Cytokine-Inducible Expression of P-Selectin in Human Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1625-1632 ◽  
Author(s):  
Lijun Xia ◽  
Junliang Pan ◽  
Longbiao Yao ◽  
Rodger P. McEver
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Proteasome Inhibitor ◽  
Sodium Salicylate ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Human Endothelial Cells ◽  
Induced Expression

Abstract Proteasome inhibitors, antioxidants, salicylates, or glucocorticoids block the cytokine-induced expression of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. These pharmacological agents have been assumed to inhibit the expression of adhesion molecules primarily by blocking activation of the transcription factor NF-κB. We found that the proteasome inhibitor ALLN, the antioxidant PDTC, or sodium salicylate, but not the glucocorticoid dexamethasone, inhibited both the constitutive and the interleukin-4– or oncostatin M–induced expression of the adhesion molecule P-selectin in human endothelial cells. ALLN, PDTC, or sodium salicylate decreased P-selectin expression without a detectable requirement for inhibition of NF-κB activation or for an intact κB element in the P-selectin gene. These results extend the potential anti-inflammatory utility of such drugs to inhibition of P-selectin expression and suggest that they have important actions that do not involve the NF-κB system.

scholarly journals A Proteasome Inhibitor, an Antioxidant, or a Salicylate, but not a Glucocorticoid, Blocks Constitutive and Cytokine-Inducible Expression of P-Selectin in Human Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1625-1632 ◽  
Author(s):  
Lijun Xia ◽  
Junliang Pan ◽  
Longbiao Yao ◽  
Rodger P. McEver
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Proteasome Inhibitor ◽  
Sodium Salicylate ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Human Endothelial Cells ◽  
Induced Expression

Proteasome inhibitors, antioxidants, salicylates, or glucocorticoids block the cytokine-induced expression of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. These pharmacological agents have been assumed to inhibit the expression of adhesion molecules primarily by blocking activation of the transcription factor NF-κB. We found that the proteasome inhibitor ALLN, the antioxidant PDTC, or sodium salicylate, but not the glucocorticoid dexamethasone, inhibited both the constitutive and the interleukin-4– or oncostatin M–induced expression of the adhesion molecule P-selectin in human endothelial cells. ALLN, PDTC, or sodium salicylate decreased P-selectin expression without a detectable requirement for inhibition of NF-κB activation or for an intact κB element in the P-selectin gene. These results extend the potential anti-inflammatory utility of such drugs to inhibition of P-selectin expression and suggest that they have important actions that do not involve the NF-κB system.

DIFFERENTIAL EFFECTS OF SHEAR STRESS ON THE EXPRESSIONS OF ICAM-1 AND VCAM-1 INDUCED BY TNF-α IN ENDOTHELIAL CELLS

2005 ◽  
Vol 05 (01) ◽  
pp. 63-79
Author(s):  
JENG-JIANN CHIU ◽  
PEI-LING LEE ◽  
SHUNICHI USAMI ◽  
SHU CHIEN
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Mrna Expression ◽  
Adhesion Molecule ◽  
Vascular Endothelial Cells ◽  
Surface Protein ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Induced Expression ◽  
Tnf Α

Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes and the adhesive function of ECs. Shear stress (20 dynes/cm2) was applied to ECs prior to or following the addition of tumor necrosis factor (TNF)-α. Shear stress increased the TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-α-induced expression of vascular adhesion molecule-1 (VCAM-1). The TNF-α-induced increase in EC adhesiveness for monocytic THP-1 cells was reduced by shear stress. After 24-h pre-shearing followed by 1 h of static incubation, the effect of pre-shearing on TNF-α-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-α-induced VCAM-1 mRNA expression following pre-shearing, however, required a static incubation time of >6 h (completely recovery at 24 h). Pre- and post-shearing caused a reduction in the nuclear factor (NF)-κB-DNA binding activity induced by TNF-α in the EC nucleus. Our findings suggest that shear stress plays differential roles in modulating the TNF-α-induced EC expressions of ICAM-1 and VCAM-1 genes, which serve similar functions in vascular biology.

Anti-Inflammatory Effects ofDanshenon Human Vascular Endothelial Cells in Culture

2013 ◽  
Vol 41 (05) ◽  
pp. 1065-1077 ◽  
Author(s):  
Christian Stumpf ◽  
Quiaoling Fan ◽  
Christian Hintermann ◽  
Dorette Raaz ◽  
Ingrid Kurfürst ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Cellular Adhesion ◽  
Tanshinone Iia ◽  
Protective Effects ◽  
Induced Expression ◽  
Tnf Α ◽  
Anti Inflammatory

Inflammation plays a crucial role in the pathophysiology of atherosclerosis. Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin play important roles as key regulators of the inflammatory process in atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine for therapy of cardiovascular diseases such as coronary artery disease. The aim of the present study was to evaluate the protective effects of DS with respect to possible anti-inflammatory effects. Human umbilical vein endothelial cells as well as platelets were incubated with an extract of DS or one of its major ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic acid (Protoc) under tumor necrosis factor (TNF)-α or ADP stimulation. Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant-protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were examined via luminex based analysis. Treatment with DS attenuated TNF-α induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced expression and release of adhesion molecules, cytokines and chemokines as well as ADP-induced expression of platelet P-selectin. Because of the key roles of inflammatory mediators in the etiology of atherosclerosis, this work provides useful insight in understanding the pharmacological efficacy of Chinese herbal medicine.

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