The Gene Expression Profile of Human Umbilical Vein Endothelial Cells Stimulated by Tumor Necrosis Factor a Using DNA Microarray Analysis

Abstract

Stimulation of vascular endothelial cells by tumor necrosis factor α (TNFα) plays a critical role in the pathogenesis of inflammation and vascular diseases. Changes in the gene expression profile in cultured human umbilical vein endothelial cells (HUVEC) treated with TNFα was analyzed with high-density oligonucleotide arrays comprised of 35, 000 genes. TNFα stimulation profoundly induced genes involved in signal transduction, leukocyte adhesion and chemoattraction. ICAM-1 mRNA (fold change 111.9) was most profoundly induced followed by TNFα receptor-associated factor 1 (TRAF1) (95.5), Bcl3 (71.8), IL8 (65. 4), fractalkaine (62.4), E-selectin (48.0), lymphotoxin, β (41.3) and VCAM-1 (31.7). In addition to these previously known genes, 18 poorly characterized or novel genes known as ESTs profoundly induced by TNFα. Initial sequencing analysis identified three of these the genes for squalene epoxydase, chromodomain helicase DNA binding protein 4, and CLP respectively. Further analysis of these genes will provide important information about TNF α signaling and function in vascular endothelial cells.