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

Inflamm Res. 2002 Jul;51(7):332-41. doi: 10.1007/pl00000312.

Abstract

Objective and design: TNF-alpha 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-alpha 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-alpha treated human endothelial cells.

Materials and methods: In this study cultured human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (10 ng/ml) for 2 and 16 h, respectively, and the gene expression pattern was profiled using a cDNA array representing 14,000 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-a 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-alpha inside the HUVECs. Expression profiling in HUVECs responding to TNF-alpha stimulation should give an understanding of the molecular mechanisms involved in vascular inflammation.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Cluster Analysis
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Female
  • Gene Expression / drug effects*
  • Genome, Human
  • Humans
  • In Situ Hybridization
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Microscopy, Electron, Scanning
  • Pregnancy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Spectrophotometry, Ultraviolet
  • Transcription, Genetic / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism*

Substances

  • Chemokine CCL2
  • DNA, Complementary
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha