BEZAFIBRATE DOWN-REGULATES FIBRINOGEN BIOSYNTHESIS IN HUMAN HEPATOMA HEPG2 CELLS

Background Bezafibrate reportedly lowers serum lipids and plasma fibri nogen in humans and rats, but the mechanism of this process has still to be clarified. We have addressed this problem by investigating the e ffects of bezafibrate on fibrinogen in the human hepatoma HepG2 cell l ine. Methods In cells cultured with and without bezafibrate, intra-and extracellular fibrinogen was quantified using an enzyme-linked immuno sorbent assay (ELISA), and changes in the biosynthesis and secretion o f bezafibrate were monitored by [S-35]-methionine labelling. In additi on, expression of the corresponding mRNA was investigated by Northern blotting. As fibrinogen is an acute-phase protein, HepG2 cells exposed to interleukin 6 were also analysed. Results Bezafibrate decreased fi brinogen biosynthesis by about 25%, regardless of whether or not the c ultures were also exposed to interleukin 6. mRNA was reduced in propor tion to the concentration of interleukin 6 to which the cells were exp osed, but intracellular transport and release of the protein were not affected. Conclusion Apparently, bezafibrate interferes with the biosy nthesis of fibrinogen at the pretranslational level but does not affec t the export of the protein.