Interleukin 1 Stimulates Endothelial Cell Tissue Factor Production and Expression by a Prostaglandin-Independent Mechanism

Abstract

SummaryActivation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.

Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide.

“…Escherichia coli is the most frequent causative agent in septic shock (2), the symptoms of which are primarily due to lipopolysaccharide (LPS). After a 4-hr incubation, LPS stimulates the generation of prostacyclin (PGI2) from endothelial cells (3)(4)(5), which may contribute to the vasodilation (through a cAMP-mediated relaxation of vascular smooth muscle) and decreased arterial blood pressure in shock (6,7).…”

Modification of Tissue-Factor mRNA and Protein Response to Thrombin and Interleukin 1 by High Glucose in Cultured Human Endothelial Cells

“…The effect of protracted exposure of endothelial cells to high glucose was also studied with respect to the procoagulant activity induced by IL-1 (29,32). In contrast with their greater tissue-factor production in response to thrombin, cultures exposed to 30 mM glucose responded to IL-1 stimulation with significantly less total tissue-factor production (cell lysates) than control cultures (P = .045; Fig.…”

“…The concentration of a-thrombin (2.5 U/ml) matched the levels generated during blood clotting (28) and was chosen after observing that concentrations between 1 and 20 U/ml induced maximal tissue-factor production. The concentration of IL-1 (5 U/ml) was chosen on the basis of reported dose responses (29).…”

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

“…These cytokines cause endothelial cell damage and downregulate the expression of TM in parallel with upregulation of TF and plasminogen activator inhibitor-1 (PAI-1) on the cell surface of endothelial cells, resulting in hypercoagulability [53,54] (Fig. 1).…”