Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression.
Oligonucleotides (ODN) expressing immunostimulatory "CpG motifs" activate human RPMI 8226 myeloma cells to secrete IL-6. Using deletion and site-directed mutagenesis of the human (h)IL-6 promoter region, two positive regulatory elements (the binding sites for the 5'-CCAAT / enhancer binding protein-beta and NF-kappaB) were identified. Two negative regulatory elements, the 3'-retinoblastoma control element (RCE) and the binding site for Epstein-Barr virus C-promoter binding factor 1 (CBF1), also contributed to CpG ODN induction of hIL-6 gene expression. Of interest, CpG ODN treatment induced the dissociation of a repressor protein from its 3'-RCE binding site. Thus, CpG ODN regulation of hIL-6 gene expression involves both enhancer and derepression mechanisms.
Takeshita
F
F
Section of Retroviral Immunology Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, USA.
Ishii
K J
KJ
Ueda
A
A
Ishigatsubo
Y
Y
Klinman
D M
DM
D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D009841:Oligonucleotides; C015772:CpG dinucleotide