Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells

The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide...

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Bibliographic Details
Published in:Thrombosis research 1995-03, Vol.77 (5), p.431-440
Main Authors: Arnman, Veronika, Stemme, Sten, Rymo, Lars, Risberg, Bo
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Blood coagulation. Blood cells
Cells, Cultured
endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Enzyme-Linked Immunosorbent Assay
fibrinolysis
Fundamental and applied biological sciences. Psychology
General aspects, investigation methods, hemostasis, fibrinolysis
Humans
Infant, Newborn
inflammatory cytokines
Interferon-gamma - pharmacology
Interleukin-6 - pharmacology
Lipopolysaccharides - pharmacology
Molecular and cellular biology
plasminogen activator
plasminogen activator inhibitor
Plasminogen Activators - drug effects
Plasminogen Activators - metabolism
Plasminogen Inactivators - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Umbilical Veins - cytology
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Summary:The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide (LPS) and tumor necrosis factor-α (TNFα) have been demonstrated to modulate the expression of fibrinolytic factors in cultured endothelial cells. In the present study the expression of tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) antigen in conditioned medium from cultured human umbilical vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was investigated under basal conditions and after stimulation with LPS, TNFα, interferon-γ (IFN-γ) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNFα increased the expression of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA response differed between the two cell types. The effects of TNFα were modulated by IFN-γ but not by IL-6. The increased expression of u-PA after stimulation with TNFα was reduced by IFN-γ. In contrast, TNFα-induced expression of PAI-2 was synergistically increased by addition of IFN-γ. These effects of IFN-γ represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.
ISSN:0049-3848
1879-2472
DOI:10.1016/0049-3848(95)93879-5