Lipopolysaccharide-induced Changes in Gene Expression in Human Lung Microvascular Endothelial Cells over Time

The vascular endothelium may play a role in the response to infectious agents and in the pathophysiology of disease processes resulting in capillary leak such as septic shock and acute respiratory distress syndrome. In order to study the effect of endotoxin on endothelial cell function, human lung microvascular endothelial cells in culture were exposed to lipopolysaccharide (LPS), 10 ng, for 4, 8, or 24 hours and changes in mRNA expression were studied using Affymetrix HG U133plus2 gene arrays. A principal components analysis revealed that LPS treatment was the primary source of variability in the data. LPS treatment of endothelial cells for 4, 8, or 24 hours resulted in the upregulation by two-fold or greater of 275, 260 and 141 genes respectively. LPS treatment resulted in the down regulation by 50% or greater of 176, 263 and 79 genes at 4, 8, or 24 hours respectively. Up regulated genes at 4 or 8 hours were enriched in those encoding for cytokines, secreted proteins, cell membrane proteins and proteins controlling signal transduction and transcriptional regulation. Down regulated genes at each of the time points included those coding for cell membrane proteins, transcriptional regulation and metabolism. At each time point, a significant proportion of the genes identified as changed were unique to that time point.

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