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Interleukin-4 stimulates expression of urokinase-type-plasminogen activator in cultured human foreskin microvascular

J Wojta1, M Gallicchio, H Zoellner

  • 1Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Blood
|June 15, 1993
PubMed

Insights

Interleukin-4 (IL-4) enhances the fibrinolytic system in human microvascular endothelial cells by increasing urokinase-type plasminogen activator (u-PA). This suggests IL-4 plays a role in angiogenesis by promoting extracellular proteolysis and cell migration.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Biochemistry

Background:

  • Endothelial cells play a crucial role in vascular homeostasis and angiogenesis.
  • The fibrinolytic system, involving enzymes like urokinase-type plasminogen activator (u-PA), regulates blood clot breakdown and extracellular matrix remodeling.
  • Interleukin-4 (IL-4) is a cytokine with known roles in immune responses and cell proliferation.

Purpose of the Study:

  • To investigate the effect of IL-4 on the fibrinolytic system of human microvascular and macrovascular endothelial cells.
  • To determine if IL-4 influences the production and activity of key fibrinolytic factors, specifically u-PA and plasminogen activator inhibitor type-1 (PAI-1).
  • To explore the potential role of IL-4 in angiogenesis through its effects on endothelial cell fibrinolysis.

Main Methods:

  • Primary human microvascular endothelial cells (from foreskin) and macrovascular endothelial cells (from saphenous vein) were cultured in vitro.
  • Cells were treated with varying doses and durations of IL-4.
  • Levels of u-PA, tissue-type plasminogen activator (t-PA), and PAI-1 were measured in cell culture supernatants and lysates using enzymatic assays and Northern blotting for mRNA analysis.

Main Results:

  • IL-4 treatment significantly increased dose- and time-dependent urokinase-type plasminogen activator (u-PA) levels in human foreskin microvascular endothelial cells (HFMEC), but not in macrovascular endothelial cells.
  • The majority of u-PA was released as the inactive single-chain form (scu-PA), which could be activated.
  • IL-4 did not affect PAI-1 levels but slightly decreased t-PA levels in HFMEC. mRNA analysis confirmed increased u-PA mRNA in HFMEC with IL-4 treatment.

Conclusions:

  • IL-4 selectively enhances the fibrinolytic potential of human microvascular endothelial cells by upregulating u-PA.
  • This modulation of the fibrinolytic system by IL-4 may contribute to its role in angiogenesis by facilitating extracellular proteolysis and cell migration.
  • The findings highlight a specific mechanism by which IL-4 influences vascular remodeling and repair processes.

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