Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 induced by tumor necrosis factor-α in human endothelial cells through the JNK/p38 pathways

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)- alpha- induced reactive oxygen species production and adhesion molecule expression and to define the mechanisms involved. SOD expression significantly suppressed TNF-alpha- induced expression of vascular cell adhesion molecule- 1 and intercellular cell adhesion molecule- 1 and reduced the binding of the human neutrophils to TNF-alpha- stimulated HAECs. SOD expression suppressed c- JUN N- terminal kinase and p38 phosphorylation. It also attenuated intracellular superoxide anion production and NADPH oxidase activity in TNF-alpha- treated HAECs. Conclusions - These results provide evidence that SOD expression in endothelial cells attenuates TNF-alpha- 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 kappaB inactivation. These results suggest that SOD has antiinflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response.