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Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells.

Abstract：

:Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Yang YY,Hu CJ,Chang SM,Tai TY,Leu SJ

doi

10.1016/j.atherosclerosis.2004.01.024

keywords:

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

207-13

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(04)00084-X

journal_volume

174

pub_type

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Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells.