Genomic-scale analysis of gene expression profiles in TNF-α treated human umbilical vein endothelial cells

Abstract.

Objective and design: TNF-α is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, and in the control of cell proliferation, differentiation and programmed cell death. However, it is known that TNF-α is also the founding member of a still growing family of cytokines with diverse bioregulative functions. Its detailed molecular mechanisms on endothelial activation and injury remain to be elucidated. This study was aimed at determining genomic-scale gene expression profiles in TNF-α treated human endothelial cells.¶Materials and methods: In this study cultured human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (10 ng/ml) for 2 and 16 h, respectively, and the gene expression pattern was profiled using a cDNA array representing 14000 gene/cDNA clusters.¶Results: In total, 72 known human genes were identified the expression levels of which altered over 2-fold in response to TNF-α stimulation. Such alteration was confirmed for IL-8 and MCP-1, with an independent quantitative mRNA assay. It was observed that genes with related biological functions were often temporally co-regulated.¶Conclusions: These results indicate the transcriptional pathways mediated by TNF-α inside the HUVECs. Expression profiling in HUVECs responding to TNF-α stimulation should give an understanding of the molecular mechanisms involved in vascular inflammation.