REGULATION OF SYNTHESIS OF SOME PROTEINASE-INHIBITORS IN HUMAN HEPATOMA-CELLS HEPG2 BY CYTOKINES, HEPATOCYTE GROWTH-FACTOR AND RETINOIC ACID

Subconfluent monolayers of human hepatoma HepG2 cells were cultured for 2 days in serum-free DMEM containing 1muM dexamethasone and human recombinant hepatocyte growth factor (HGF), retinoic acid (RA), IL-1, IL-6, LIF and mixtures of these factors. Incorporation of labelled thymidine was significantly decreased by IL-6, IL-1 and HGF but only slightly by LIF and RA. Synthesis of acute phase proteins secreted daily to the media was measured by electroimmunoassay with monospecific antisera. In addition, the synthesis and secretion of some proteinase inhibitors (alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, C1-inactivator, plasminogen activator inhibitor-1, inter-alpha-trypsin inhibitor and pre-alpha-inhibitor) was evaluated by incorporation of labelled methionine and fluorography. Among the cytokines tested IL-6 was the most potent regulator of acute phase protein synthesis. Hepatocyte growth factor stimulated basal synthesis of alpha-1-antichymotrypsin, and to a lesser extent affected some other proteins. Retinoic acid preferentially increased synthesis of alpha-1-antichymotrypsin, ceruloplasmin and plasminogen activator inhibitor-1. Both HGF and RA slightly modulated cytokine-induced synthesis of several acute phase proteins in HepG2 cells.