Transient overexpression of human 15-lipoxygenase in aortic endothelial cells enhances tumor necrosis factor-induced vascular cell adhesion molecule-1 gene expression.
15-lipoxygenase (15-LO) expression in artery wall cells has been demonstrated during the development of atherosclerosis in various animal models. We examined whether the expression of 15-LO in aortic endothelial cells affects the gene expression of the adhesion molecule, vascular cell adhesion molecule-1 (VCAM-1). Transient transfection of human 15-LO cDNA into bovine aortic endothelial cells led to the expression of 15-LO protein and enzymatic activity. We studied the induction of VCAM-1 mRNA in these cells. 15-LO expressing cells showed no detectable levels of VCAM-1 message. However, when TNF was added to these cells there was a synergistic increase in VCAM-1 expression relative to cells that were transfected with control plasmid pcDNA I. Our data suggest that 15-LO expression in aortic endothelium may amplify the expression of VCAM-1 induced by inflammatory stimulus during atherogenesis.
Wölle
J
J
Department of Atherosclerosis Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan, 48105, USA.
Welch
K A
KA
Devall
L J
LJ
Cornicelli
J A
JA
Saxena
U
U
D000818:Animals; D000991:Antithrombins; D001011:Aorta; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008041:Linoleic Acids / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D000991:Antithrombins; D008041:Linoleic Acids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C024348:13-hydroxy-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase