scholarly journals Tumor Necrosis Factor α Activates the Human Plasminogen Activator Inhibitor-1 Gene through a Distal Nuclear Factor κB Site

2004 ◽  
Vol 279 (18) ◽  
pp. 18127-18136 ◽  
Author(s):  
Baidong Hou ◽  
Mesut Eren ◽  
Corrie A. Painter ◽  
Joseph W. Covington ◽  
John D. Dixon ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Plasminogen Activator Inhibitor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Plasminogen ◽  
Factor Α ◽  
Activator Inhibitor ◽  
Necrosis Factor

The Endotoxin-induced Plasminogen Activator Inhibitor-1 Increase in Rabbits Is Not Tumor Necrosis Factor-α Dependent and Can Occur in the Absence of Interleukin-1β

2002 ◽  
Vol 88 (10) ◽  
pp. 639-643 ◽  
Author(s):  
Ramón Montes ◽  
Pablo Rodríguez-Whilhelmi ◽  
Verónica Hurtado ◽  
Akihiro Matsukawa ◽  
Marta Montes ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

SummaryThe plasminogen activator inhibitor-1 (PAI-1)-dependent fibrinolytic inhibition occurring in endotoxemia contributes to disseminated intravascular coagulation (DIC). Previous findings suggest that tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are responsible for the increase in the level of PAI-1. These observations usually arose from mild endotoxemia models. We analyzed the effect of FR167653, an inhibitor of the TNF-α/IL-1β production, on the PAI-1 levels in rabbits given endotoxin at a dose sufficient to induce DIC: the steep plasma PAI-1 increase was not attenuated by FR167653, in spite of achieving efficient inhibition of the TNF-α production. No IL-1β was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF-α and IL-1β. If these findings applied to humans, therapeutic intervention directing these cytokines would not be useful for the treatment of fibrinolysis in patients with severe sepsis.

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