Regulation of expression of the complement factor H gene in a murine liver cell line by interferon-gamma.
Factor H is a regulatory protein of the alternative pathway of complement activation that is synthesized mainly in the liver. The authors used the +/+ Li murine liver cell line as a model for examining its regulation. When +/+ Li cells were incubated with IFN-gamma, the levels of factor H mRNA increased in a dose-dependent manner, achieving a maximal response at a concentration of 50-100 units/ml. The increase in factor H mRNA levels was paralleled by an increase in factor H secretion. The kinetics of induction of factor H mRNA were slow, with the response reaching near maximal levels at 24 h. The increase in factor H mRNA by IFN-gamma was dependent on protein synthesis, as cycloheximide abolished the response. The presence of IFN-gamma was required for the entire incubation period in order to produce a maximal response. The luciferase system was used in an attempt to identify an interferon-responsive element. Luciferase constructs containing from 807 to 236 bp of upstream sequence responded to IFN-gamma with a twofold induction of luciferase activity, whereas a construct containing 83 bp of 5' sequence did not. Thus, IFN-gamma stimulates factor H mRNA transcription through a protein intermediary that interacts with the promoter between positions -83 and -236.
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Department of Microbiology and Immunology, University of New Mexico School of Medicine, Albuquerque 87131-5276, USA.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017242:Complement Factor H / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007371:Interferon-gamma / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D015533:Transcriptional Activation
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D017242:Complement Factor H; D007371:Interferon-gamma; D004247:DNA; D003513:Cycloheximide; D008156:Luciferases