Cytokine regulation of the synthesis of plasminogen activator inhibitor-2 by human vascular endothelial cells. Comparison with plasminogen activator inhibitor-1 synthesis.
Plasminogen activators are inhibited by plasminogen activator inhibitors-1 (PAI-1) and -2 (PAI-2). We describe the synthesis of PAI-2 by human vascular endothelial cells (EC) cultured from umbilical vein, saphenous vein and foreskin microvasculature in response to interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF alpha) and compare it with that of PAI-1. Both PAI-2 and PAI-1 were quantitated by ELISAs. PAI-2 was cell-associated while PAI-1 was secreted by EC. IL-1 alpha and TNF alpha increased the synthesis of PAI-2 and PAI-1 by EC in a dose-dependent manner. IL-1 alpha was a stronger stimulus for PAI-2 synthesis than TNF alpha, while both cytokines were equally effective for PAI-1. Northern blot analysis revealed similar changes in mRNA levels to those in antigen levels. PAI-2 synthesis by cytokine-stimulated EC may be important in thrombus formation and inflammation.
Zoellner
H
H
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Vic., Australia.
Wojta
J
J
Gallicchio
M
M
McGrath
K
K
Hamilton
J A
JA
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate