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

Shing Jong Lin, Song Kun Shyue, Ya Yun Hung, Yung Hsiang Chen, Hung Hai Ku, Jaw Wen Chen, Ka Bik Tam, Yuh Lien Chen

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

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)-α-induced reactive oxygen species production and adhesion molecule expression and to define the mechanisms involved. SOD expression significantly suppressed TNF-α-induced expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and reduced the binding of the human neutrophils to TNF-α-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-α-treated HAECs. Conclusions - These results provide evidence that SOD expression in endothelial cells attenuates TNF-α-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 κB inactivation. These results suggest that SOD has antiinflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response.

Original languageEnglish
Pages (from-to)334-340
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2005
Externally publishedYes

Keywords

  • Adhesion molecule
  • Atherosclerosis
  • Endothelial cell
  • MAPKs
  • Superoxide dismutase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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