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

Busso, Nathalie
Nicodeme, E.
Chesne, C.
Guillouzo, A.
Hyafil, F.
Published in Hepatology. 1994, vol. 20, no. 1 Pt 1, p. 186-190
Abstract We examined the effects of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-beta) 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-1 beta and tumor necrosis factor-alpha 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-1 beta and tumor necrosis factor-alpha) 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-beta 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-beta may play a critical role in hepatic pathophysiology.
Keywords Cells, CulturedCytokines/ pharmacologyHumansInflammation/ metabolismInterleukin-1/pharmacologyLiver/cytology/ metabolismPlasminogen Activator Inhibitor 1/ biosynthesis/geneticsRNA, Messenger/metabolismTissue Plasminogen Activator/biosynthesisTransforming Growth Factor beta/pharmacologyTumor Necrosis Factor-alpha/pharmacologyUrokinase-Type Plasminogen Activator/ biosynthesis/genetics
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PMID: 8020888
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