Regulation of tissue factor gene expression in human monocytic and endothelial cells

Tissue factor (TF) is inducibly expressed within the vasculature by monocytes and endothelial cells. Transcriptional activation of the TF gene in these two cell types by bacterial lipopolysaccharide (LPS) or cytokines appears to be regulated by a common mechanism. Functional studies identified a 56-bp LPS response element which contains two AP-1 sites and a kappaB site. Assembly of a multiprotein complex composed of Fos-Jun and c-Rel-p65 heterodimers is required to induce TF gene transcription. Inhibiting proteolytic degradation of IkappaBalpha prevents nuclear translocation of c-Rel-p65 heterodimers and blocks inducible TF expression in monocytic and endothelial cells.