The dynamics of gene expression in human lung microvascular endothelial cells after stimulation with inflammatory cytokines

Vascular endothelium plays an essential role in the pathogenesis or vasoocclusion. The changes in the endothelial cell function can be triggered by changes in gene expression caused by interaction with cytokines and blood cells. Using cDNA arrays, we have recently reported complex patterns of gene expression after stimulation of endothelial cells with TNF alpha and IL-1 beta. Better understanding of the time course of gene expression changes, their concentration dependence and reversibility after withdrawal of the offending cytokine is essential for successful prevention and therapy of vasoocclusion. Here we present a detailed study of the concentration dependence and time Course of gene expression in endothelial cells after their exposure to TNFa and IL-1 beta. We focus oil the adhesion molecules (VCAM-1, ICAM-1, E-selectin) and cytokines (IL-6, GCP-2, MCP-1) that are likely to contribute to vasoocclusion. We report differences in the time Course and intensity of their expression and in their response to TNF alpha and IL-10 stimulation. We demonstrate that expression of the studied genes is upregulated by low TNF alpha concentrations that better reflect the TNF alpha levels detected in the plasma of patients developing vasoocclusion. These results help to understand the changes in the endothelium and to design rational prevention and therapy of vasoocclusion.