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Regulation of Expression of the Complement Factor H Gene in a Murine Liver Cell Line by Interferon‐γ
Author(s) -
VIK D. P.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-299.x
Subject(s) - biology , interferon , gene , complement (music) , gene expression , cell culture , virology , immunology , complement factor i , interferon regulatory factors , complement system , microbiology and biotechnology , genetics , transcription factor , antibody , phenotype , complementation
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‐γ, 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‐γ was dependent on protein synthesis, as cycloheximide abolished the response. The presence of IFN‐γ 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‐γ with a twofold induction of luciferase activity, whereas a construct containing 83 bp of 5′ sequence did not. Thus, IFN‐γ stimulates factor H mRNA transcription through a protein intermediary that interacts with the promoter between positions −83 and −236.