on December 2, 2004
Published online before print December 2, 2004, doi: 10.1161/01.ATV.0000152114.00114.d8
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Submitted on February 5, 2004
Accepted on November 3, 2004
Superoxide Dismutase Inhibits the Expression of Vascular Cell Adhesion Molecule-1 and Intracellular Cell Adhesion Molecule-1 Induced by Tumor Necrosis Factor-
in Human Endothelial Cells Through the JNK/p38 Pathways
Shing-Jong Lin ;
From the Institute of Clinical Medicine (S.-J.L., Y.-H.C., J.-W.C.), Cardiovascular Research Center (S.-J.L.), and the Institute of Anatomy and Cell Biology (Y.-Y.H., H.-H.K., Y.-L.C.), National Yang-Ming University; the Institute of Biomedical Science (S.-K.S., K.-B.T.), Academia Sinica; and the Division of Cardiology (S.-J.L., J.-W.C.), Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
* To whom correspondence should be addressed. E-mail: chenyl{at}ym.edu.tw.
Objective--Expression of adhesion molecules on endothelial cells and subsequent leukocyte recruitment are critical early events in the development of atherosclerosis. We tried to study possible effects of Cu/Zn superoxide dismutase (SOD) on adhesion molecule expression and its underlying mechanism in the prevention and treatment of cardiovascular disorders.
Methods and Results--Human aortic endothelial cells (HAECs) were transfected with adenovirus carrying the human SOD gene (AdSOD) to investigate whether SOD expression in HAECs attenuated tumor necrosis factor (TNF)-
-induced reactive oxygen species production and adhesion molecule expression and to define the mechanisms involved. SOD expression significantly suppressed TNF--induced expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and reduced the binding of the human neutrophils to TNF--stimulated HAECs. SOD expression suppressed JNK and p38 phosphorylation. It also attenuated intracellular superoxide anion production and NADPH oxidase activity in TNF--treated HAECs.
Conclusions--These results provide evidence that SOD expression in endothelial cells attenuates TNF--induced superoxide anion production and adhesion molecule expression, and that this protective effect is mediated by decreased JNK and p38 phosphorylation and activator protein-1 and nuclear factor 
B inactivation. These results suggest that SOD has antiinflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response.
Key words: superoxide dismutase • atherosclerosis • endothelial cell • adhesion molecule • MAPKs
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