- 日本網内系学会会誌 (ISSN:03869725)
- vol.31, no.4, pp.345-353, 1991 (Released:2009-06-04)
Influence of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) on the expression of thrombomodulin (TM, anticoagulant factor) and tissue factor-like procoagulant activity (PA, procoagulant factor) on cultured human umbilical vein endothelial cells and the effect of retinoic acid (RA, vitamin A acid) on the behavior of TM and PA in the cells caused by the cytokines were investigated. TNF-α and IL-1β induced the reduction of TM expression and elevation of PA in the cells in a dose-dependent manner in a range between 1 and 100U/ml. The reduction of TM expression by the cytokines accompanied with the decrease in TM mRNA levels, and the elevation of PA was inhibited by treatment with cycloheximide, inhibitor for protein synthesis. The current results indicate that the cytokines markedly increase procoagulant properties on the cell membrance through both the reduction of anticoagulant factor and the elevation of procoagulant factor, and suggest that the behaviors of anti- and pro-coagulant factor caused by the cytokines results from changes in protein synthesis. Treatment of the cells with RA prevented both the reduction of TM expression and the elevation of PA on the cell membrane caused by TNF-α treatment, in a dose-dependent manner in a range between 0.01 and 10μM. RA increased TM mRNA levels in the cells. It was suggested that RA regulates the balance between the expression of anti- and pro-coagulant factors on the cell membrance through regulation of gene transcription levels.