THE PRODUCTION OF HEPARIN-COFACTOR-II IS NOT REGULATED BY INFLAMMATORY CYTOKINES IN HUMAN HEPATOMA-CELLS - COMPARISON WITH PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1

Using the Northern blot technique, we screened 6 human hepatoma cell l ines to investigate the regulation mechanism of heparin cofactor II (H C II) biosynthesis. We found that HuH-7 and Hep G2 cells constitutivel y expressed the HC II gene. In conditioned medium, HuH-7 cells constan tly produced HC II that was functionally active and formed a complex w ith thrombin in the presence of dermatan sulfate. HC II is thought be an acute phase reactant, and, therefore, we examined the effects of th e major inflammatory cytokines, IL-6, IL-1 beta, and TNF-alpha, on the regulation of HC II production in HuH-7 and Hep G2 cells. In HuH-7 ce lls, the antigen and mRNA levels of plasminogen activator inhibitor ty pe-1 (PXI-1), an acute phase protein produced by hepatocytes, were inc reased in response to stimulation with either IL-6 or IL-1 beta or bot h, but HC II antigen and mRNA levels were not changed by the same stim ulation. Even when Hep G2 cells were treated with a combination of thr ee cytokines, IL-6, IL-1 beta, and TNF-alpha, HC II antigen and mRNA l evels were not changed: however, PAI-1 antigen and mRNA levels were cl early increased. These results suggest that the production of HC II in hepatoma cells is not regulated by the major inflammatory mediators, IL-6, IL-1 beta, and TNF-alpha.