CpG ODN-mediated regulation of IL-12 p40 transcription.
Oligodeoxynucleotides (ODN) containing CpG motifs activate RAW 264.7 mouse macrophages and RPMI 8226 human myeloma cells to produce IL-12 p40. Using deletion and site-directed mutagenesis, the nuclear factor (NF)-kappaB half-site and the CCAAT/enhancer binding protein (C/EBP) recognition site were identified as potent cis-acting elements in CpG ODN-mediated IL-12 p40 promoter activation. Several NF-kappaB/Rel proteins competed for binding to the NF-kappaB half-site. The p65/c-Rel and p65/p50 heterodimer occupied this site shortly after CpG ODN administration (0.5-2 h), while the p50/c-Rel heterodimer dominated binding in the late stage (8-12 h). The induction of p50/c-Rel heterodimer was associated with a significant expression of IL-12 p40 mRNA. C/EBPbeta also contributed to CpG ODN-mediated IL-12 p40 promoter activation.
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda 20892, USA.
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Klinman
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D022762:CCAAT-Enhancer-Binding Proteins; C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D020569:Proto-Oncogene Proteins c-rel; D013873:Thionucleotides; D051996:Transcription Factor RelA; D018664:Interleukin-12