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Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: Modulation by inflammatory agents
Author(s) -
Busso Nathalie,
Nicodeme Edwige,
Chesne Christophe,
Guillouzo André,
Belin Dominique,
Hyafil François
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840200128
Subject(s) - plasminogen activator , urokinase , activator (genetics) , pharmacology , medicine , chemistry , cancer research , receptor
We examined the effects of inflammatory cytokines (interleukin‐1β, tumor necrosis factor‐α and transforming growth factor‐β) on the plasminogen activator system (urokinase, tissue‐type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleuklin‐1β and tumor necrosis factor‐α 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‐1β and tumor necrosis factor‐α) 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‐β 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‐β may play a critical role in hepatic pathophysiology. (Hepatology 1994;20:186–190.)