Tumor necrosis factor enhances expression of tissue factor mRNA in endothelial cells

We have examined the effect of recombinant tumor necrosis factor on the expression of tissue factor activity and tissue factor mRNA levels in vascular endothelial cells. Following exposure of human umbilical vein endothelial cells to this cytokine, the appearance of tissue factor procoagulant activity was detected following cell disruption, and was maximal at 6 hours. Northern blot analysis of cytokine-treated cells demonstrated a similar increase in the synthesis of tissue factor mRNA, followed by a gradual decline to the basal level by 18 hours. Cycloheximide by itself induced the accumulation of high levels of tissue factor mRNA in these cells. This result suggests that the proteins necessary for transcription of the tissue factor gene are present in the endothelial cell prior to cytokine stimulation, and synthesis of the tissue factor mRNA may be controlled, in part, by a labile repressor protein.