Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: Modulation by inflammatory agents

✍ Scribed by Nathalie Busso; Edwige Nicodeme; Christophe Chesne; André Guillouzo; Dominique Belin; François Hyafil

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 622 KB
• Volume: 20
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840200128

✦ Synopsis

We examined the effects of inflammatory cytokines (interleukin-lp, tumor necrosis factor-a and transforming growth factor+) on the plasminogen activator system (urokinase, tissue-type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleukin-lp and tumor necrosis factor-a increase urokinase-type plasminogen activator production, reinforcing the concept that increased urokinase production is associated with inflammatory processes. By contrast, the same agents (i.e., interleukin-1p and tumor necrosis factor-a) do not stimulate plasminogen activator inhibitor type 1 production. This latter observation rules out hepatocytes as a major cellular source of plasmatic plasminogen activator inhibitor type 1 during acute-phase-related responses. Among the inflammatory agents used, transforming growth factor$ was found to be the most effective modulator of both urokinase-type plasminogen activator and plasminogen activator inhibitor type 1, inducing severalfold increases of activity of urokinase-type plasminogen activator, antigen and the corresponding mRNA and increasing plasminogen activator inhibitor type 1 antigen and mRNA levels. Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 modulation by transforming growth factor-p may play a critical role in hepatic pathophysiology. (HEPATOLOGY 1994;20:186-190.) Plasminogen activators are serine proteases that initiate fibrinolysis by converting the zymogen plasminogen into the active enzyme plasmin. Two different plasminogen activators (PAS), which are the products of two distinct genes, have been characterized (1). Tissue-type PA (t-PA) is considered to play a critical role in the onset of thrombolysis (2), whereas urokinase-type