Induction of plasminogen activator inhibitor 1 biosynthesis by hyperthermia

✍ Scribed by Gabriela E. Bergonzelli; Egbert K. O. Kruithof

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 885 KB
• Volume: 148
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041480217

✦ Synopsis

Abstract

Hyperthermia is a clinical sign of inflammation and constitutes in itself an adaptive defense mechanism. The fibrinolytic system, a highly regulated proteolytic system, a involved in inflammatory processes. Plasminogen activator inhibitor 1 (PAI‐1) is the principal inhibitor of the two activators of the fibrinolytic system: tissue‐ and urokinase‐type PAs (t‐PA and u‐PA). Our present paper provides the first evidence that hyperthermia can directly induce PAI‐1. A moderate heat stress, sufficient to induce heat shock protein 70 mRNA approximately 100‐fold, resulted in a two‐to three‐fold increase in functionally active PAI‐1 in the conditioned medium of human HT‐1080 fibrosarcoma and Hep G2 hepatoma cells. Exposure of these cells to 42°C led to a similar two‐fold and two‐to five‐fold induction of PAI‐1 mRNA expression in HT‐1080 and Hep G2 cells, respectively, as has been determined by using both oligo d(T) selected and total RNA preparations. These results suggest that the observed increase in PAI‐1 accumulation is due to an induction of PAI‐1 biosynthesis. Run‐on transcription analysis indicates that the induction of PAI‐1 biosynthesis by hyperthermia is mediated by a stimulation of PAI‐1 gene transcription. No significant effect of hyperthermia was found on t‐PA or u‐PA at the level of antigen accumulation, mRNA, and gene transcription in human HT‐1080 fibrosarcoma cells. These results point to an additional regulatory mechanism of fibrinolysis in the context of inflammation.