Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression

Oligonucleotides (ODN) expressing immunostimulatory "CpG motifs" activate h uman RPMI 8226 myeloma cells to secrete IL-6. Using deletion and site-direc ted mutagenesis of the human (h)IL-6 promoter region, two positive regulato ry elements (the binding sites for the 5'-CCAAT/enhancer binding protein-be ta and NF-kappa B) were identified. Two negative regulatory elements, the 3 '-retinoblastoma control element (RCE) and the binding site for Epstein-Bar r virus C-promoter binding factor 1 (CBF1), also contributed to CpG ODN ind uction of hIL-6 gene expression. Of interest, CpG ODN treatment induced the dissociation of a repressor protein from its 3'-RCE binding site. Thus, Cp G ODN regulation of hIL-6 gene expression involves both enhancer and derepr ession mechanisms.