gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes.
gamma-Interferon (IFN-gamma) is a well characterized lymphokine known to regulate many mononuclear phagocyte functions, including expression of class I and class II major histocompatibility complex genes. The second component of complement (C2) and factor B are major histocompatibility complex class III gene products synthesized in mononuclear phagocytes. Recombinant IFN-gamma increased the synthesis of C2 and factor B in primary cultures of human mononuclear phagocytes and in murine fibroblasts transfected with cosmid DNA bearing the human C2 and factor B genes. In both cell types the increases in C2 and factor B protein synthesis were detected at concentrations of IFN-gamma less than 1 unit/ml and the regulation of each was pretranslational. The IFN-gamma-induced increases in C2 and factor B mRNA did not require new protein synthesis. In primary cultures of human monocytes, the kinetics of induction of C2 and factor B synthesis differed, but in the transfected L-cells the kinetics were similar, suggesting differences in transduction of the IFN-gamma signal, transcriptional, and/or post-transcriptional events in the two cell types. The small size of the factor B 5' flanking region, which is bounded by the 3' terminus of the IFN-gamma-regulated C2 gene, provides a well defined region to probe the structural basis for IFN-gamma regulation of gene expression.
Strunk
R C
RC
Cole
F S
FS
Perlmutter
D H
DH
Colten
H R
HR
D000818:Animals; D003175:Complement C2 / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008895:Milk, Human / Q000032:analysis; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D003175:Complement C2; D012333:RNA, Messenger; D011061:Poly A; D007371:Interferon-gamma; D004247:DNA; D003513:Cycloheximide