Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes

doi:10.1084/jem.168.2.751

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Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes

RL Medcalf, EK Kruithof and WD Schleuning
Central Hematology Laboratory, University of Lausanne Medical School, Switzerland.

Human rTNF/Cachectin was shown to stimulate gene transcription of plasminogen activator inhibitor (PA1)-1 and PAI-2, and simultaneously suppress constitutive gene expression of tissue-type plasminogen activator (t-PA) in human fibrosarcoma cells. We propose that a TNF- mediated reprogramming of gene transcription induces, in appropriate target cells, an anti-fibrinolytic state, which may cooperate with the induction of procoagulant activity (tissue factor) to stabilize the fibrin deposits commonly found in inflamed tissue. PAI genes also provide a model system for a study of the molecular pathways underlying TNF-mediated signal transduction.
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