Constitutive plasminogen activator inhibitor 1 (PAI-1) biosynthesis in human Hep G2 hepatoma cells is maintained by an autocrine factor.
We studied the production of PAI-1 by human Hep G2 hepatoma cells. When culturing these cells in fresh medium (FM), PAI-1 accumulation rate was not linear: PAI-1 antigen after 24 h was 200 ng/10(6) cells while in subsequent 24 h periods, it was on average 1,000 ng/10(6) cells. Culture of Hep G2 cells in regular changes of a 12 h conditioned medium (CM) obtained from other Hep G2, instead of in FM, resulted in a 2-fold higher PAI-1 accumulation. In cells incubated in FM, PAI-1 mRNA declined rapidly after medium change and returned to basal levels after 24 h. In contrast, PAI-1 mRNA remained relatively stable when CM was used. The acute phase mediator interleukin 6 (IL-6) was not responsible for the autocrine stimulation of PAI-1: neither IL-6 nor antibodies to IL-6 altered the observed variations in PAI-1 expression. Our studies suggest the presence of an unknown PAI-1 stimulating factor.
Bergonzelli
G E
GE
Department of Medicine, University Hospital, Lausanne, Switzerland.
Kruithof
E K
EK
D001685:Biological Factors / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003470:Culture Media; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D001685:Biological Factors; D003470:Culture Media; D005340:Fibrinogen; D015850:Interleukin-6; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors