LIPOPOLYSACCHARIDE-MEDIATED TRANSCRIPTIONAL ACTIVATION OF THE HUMAN TISSUE FACTOR GENE IN THP-1 MONOCYTIC CELLS REQUIRES BOTH ACTIVATOR PROTEIN-1 AND NUCLEAR FACTOR-KAPPA-B BINDING-SITES

Lipopolysaccharide (LPS) activation of cells of monocytic lineage leads to rapid and transient expression of a set of inflammatory gene products, including tissue factor (TF). This transmembrane receptor is the major cellular initiator of the blood coagulation cascades, and induced expression of TF is postulated to play a role in inflammation. Functional studies using transfected THP-1 monocytic cells revealed the presence of a 56-bp LPS response element (LRE) within the TF promoter that conferred LPS responsiveness to a heterologous promoter. LPS stimulation of these cells activated proteins that bound to nucleotide sequences within the LRE resembling consensus binding sites for activator protein 1 (AP-1) and nuclear factor kappa-B (NF-kappa-B). Induction of the TF gene may represent a prototypic example of gene activation in monocytic cells by assembly of transcription factor complexes, and may clarify the role of AP-1 and NF-kappa-B in the regulation of other LPS-responsive genes.