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 activation. 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 interferon-gamma (IFN-gamma). The maximal response was achieved at 50 U/ml of IFN-gamma. An increase in H mRNA was observed as early as 2 h after addition of IFN-gamma; the response peaked at 24 h. The half-life of H mRNA in the presence 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 manner with increasing concentrations of CHX. Phosphorylation events were also important in this induction because the kinase inhibitors staurosporine and genistein inhibited the induction of H mRNA by 88% and 68%, respectively. The induction could be inhibited completely when Hep3b cells were treated with CHX and staurosporine. Thus induction of factor H by IFN-gamma apparently involves two factors. One is likely to be Stat1alpha and the other is a CHX-sensitive protein.
D017242:Complement Factor H / Q000096:biosynthesis* / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured