Interleukin-1, endotoxin or tumor necrosis factor/cachectin enhance the level of plasminogen activator inhibitor messenger RNA in bovine aortic endothelial cells.
It is known that either endotoxin (LPS) or interleukin-1 (IL-1) increase the activity of plasminogen activator inhibitor (PAI) in the culture media of human and bovine endothelial cells. We have confirmed these results in bovine aortic endothelial cells (BAEC). To determine if this effect was mediated by increases in the level of PAI messenger RNA (mRNA) we examined the effects of these cytokines on PAI mRNA levels in BAEC, using RNA blot analyses. Treatment of BAEC with either IL-1, LPS, or human recombinant tumor necrosis factor/cachectin (TNF) dramatically increased the level of PAI mRNA. Since elevated levels of PAI will decrease fibrinolytic potential, this mechanism is in concert with the known increase in in vivo procoagulant potential induced by these agents and could contribute to thromboembolic phenomena.
Medina
R
R
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.
Socher
S H
SH
Han
J H
JH
Friedman
P A
PA
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D012333:RNA, Messenger / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004731:Endotoxins; D006023:Glycoproteins; D007375:Interleukin-1; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010960:Plasminogen Activators