Effects of ibuprofen on the synthesis of Plasminogen Activator Inhibitor-1 in cultured endothelial cells
Danuta Zapolska-Downar, Andrzej Zapolski-Downar, Andrzej Modrzejewski, Janina Zawierta, Marek Naruszewicz
Med Sci Monit 1999; 5(3): BR428-433
Endothelial cells play an important role in the regulation of inflammatory processes and fibrinolytic activity. When stimulated by inflammatory cytokines they respond by increased synthesis of the plasminogen activator inhibitor (PAI-1). This study assessed the influence of ibuprofen on interleukin-1β (IL-1β), tumor necrosis factor α (TNFα)-stimulated PAI-1 and reactive oxygen species (ROS) overproduction by cultured endothelial cells. Endothelial cells exposed to TNFα or IL-1β in combination with ibuprofen produced smaller amounts of PAI-1 than cells cultured with cytokines only. The suppressive activity of ibuprofen on PAI-1 synthesis stimulated by cytokines depended on its dose and magnitude of cell stimulation. Ibuprofen alone had no influence on the synthesis of PAI-1 by unstimulated endothelial cells. Both TNFα and IL-1β increased cellular oxidation. Pretreatment with ibuprofen attenuated the cytokine-mediated increase in ROS production by cultured endothelial cells. The observed influence of ibuprofen on the production of PAI-1 by endothelial cells may have important clinical implications, since many inflammatory processes evolve with decreased fibrinolytic activity accompanied by elevated PAI-1 serum levels.
Keywords: intracellular reactive oxygen species, plasminogen activator inhibitor-1, Ibuprofen, Interleukin-1beta, Tumor Necrosis Factor-alpha, endothelial cells