Regulation of complement factor H in a human liver cell line by interferon-gamma

Factor H is a regulatory protein of the alternative pathway of complement a ctivation. The liver is the major site of synthesis. We have used the Hep3b human liver cell line as a model for examining its regulation by interfero n-gamma (IFN-gamma). The maximal response was achieved at 50 U/ml of IFN-ga mma. An increase in H mRNA was observed as early as 2 h after addition of I FN-gamma; the response peaked at 24 h. The half-life of H mRNA in the prese nce of IFN-gamma was 3.8 +/- 0.8 h. The increase in H mRNA by IFN-gamma was partly dependent on protein synthesis, as cycloheximide (CHX) reduced the response by 40% and the level of H mRNA decreased in a dose-dependent manne r with increasing concentrations of CHX. Phosphorylation events were also i mportant in this induction because the kinase inhibitors staurosporine and genistein inhibited the induction of H mRNA by 88% and 68%, respectively. T he induction could be inhibited completely when Hep3b cells were treated wi th CHX and staurosporine. Thus induction of factor H by IFN-gamma apparentl y involves two factors. One is likely to be Stat1 alpha and the other is a CHX-sensitive protein.