Interleukin-1-mediated enhancement of mouse factor B gene expression via NF kappa B-like hepatoma nuclear factor.
Complement factor B, a serine protease playing a pivotal role in alternative pathway activation, is an acute-phase plasma protein. Previous studies have revealed that interleukin-1 (IL-1) mediates, at least in part, the acute-phase induction of factor B expression and that the IL-1-responsive element resides in the region between -553 and -478 relative to the transcription initiation site of the mouse factor B gene. In this paper, we demonstrate a specific binding site for a nuclear factor of human hepatoma HepG2 cells in this region of the factor B gene, using gel shift and methylation interference analysis. The nucleotide sequence of the binding site is closely similar to the NF kappa B or H2TF1 binding motif. The binding activity of HepG2 showed very similar specificity to that of NF kappa B or H2TF1, as shown by a competition binding assay, and was induced by IL-1 alpha treatment. A synthetic oligonucleotide corresponding to this binding site, as well as a similar sequence found in another class III complement C4 gene, conferred IL-1 responsiveness on the minimal factor B promoter. In contrast, a mutated oligonucleotide that could not bind to the HepG2 nuclear factor did not confer IL-1 responsiveness. These results suggest that IL-1 induces factor B expression via NF kappa B or a closely related factor in hepatocyte nuclei.
Nonaka
M
M
Department of Immunobiology, Kanazawa University, Japan.
Huang
Z M
ZM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008113:Liver Neoplasms; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015345:Oligonucleotide Probes; D010957:Plasmids
D007375:Interleukin-1; D016328:NF-kappa B; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011415:Complement Factor B