Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells
Arnman, V.; Stemme, S.; Rymo, L.; Risberg, B.
Thrombosis Research 77(5): 431-440
1995
ISSN/ISBN: 0049-3848 PMID: 7778058 Document Number: 446458
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-alpha (TNF-alpha) 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, TNF-alpha, interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF-alpha 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 TNF-alpha were modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF-alpha was reduced by IFN-gamma. In contrast, TNF-alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma. These effects of IFN-gamma represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.