Lin S.-J.Shyue S.-K.Hung Y.-Y.Chen Y.-H.Ku H.-H.Chen J.-W.Tam K.-B.YUH-LIEN CHEN2020-03-032020-03-0320051079-5642https://www.scopus.com/inward/record.uri?eid=2-s2.0-13244270147&doi=10.1161%2f01.ATV.0000152114.00114.d8&partnerID=40&md5=57d0eea5f861135a0a1861bd9c08f404https://scholars.lib.ntu.edu.tw/handle/123456789/468559Objective - 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.[SDGs]SDG3adenovirus vector; copper zinc superoxide dismutase; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; mitogen activated protein kinase p38; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; stress activated protein kinase; superoxide; transcription factor AP 1; tumor necrosis factor alpha; vascular cell adhesion molecule 1; antiinflammatory activity; aorta; article; atherosclerosis; cardiovascular disease; cell adhesion; endothelium cell; enzyme phosphorylation; gene expression; genetic transfection; human; human cell; leukocyte; neutrophil; priority journal; protein expression; viral gene therapy; Anthracenes; Aorta; Arteriosclerosis; Cell Adhesion; Depression, Chemical; Endothelial Cells; Endothelium, Vascular; Flavonoids; Gene Expression Regulation; Humans; Imidazoles; Inflammation; Intercellular Adhesion Molecule-1; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; NADPH Oxidase; Neutrophils; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Processing, Post-Translational; Pyridines; Recombinant Fusion Proteins; Superoxide Dismutase; Superoxides; Transcription Factor AP-1; Transcription, Genetic; Transduction, Genetic; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1journal article10.1161/01.ATV.0000152114.00114.d8155766392-s2.0-13244270147