Aspirin inhibits monocyte chemoattractant
protein-1 and interleukin-8 expression in
TNF-a stimulated human umbilical vein
endothelial cells
呂思潔
Yang YY;Hu CJ;Chang SM;Tsi TY;Leu SJ
摘要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 (10ng/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 lowas 10microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% ( [Formula: see text] ) and IL-8 by 26.9% ( [Formula: see text] ) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 ( [Formula: see text] ) and IL-8 ( [Formula: see text] ). Furthermore, aspirin (10microg/ml) inhibited U937 cell adhesion by a 13.4% ( [Formula: see text] ) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration,aspirin also inhibited U937 migration to HUVEC by 89.1% ( [Formula: see text] ) 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.
