NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site.

摘要: In these studies, we show that NF-kappa B induces transcription from the human pro-IL-1 beta (IL-1 beta) gene. A recombinant plasmid pIL-1(-4000)-CAT, containing 4 kb of IL-1 gene upstream regulatory sequence was transactivated by p65 subunit or treatment cells with a combination inducers including LPS, PMA, and dibutyryl cyclic AMP (L+P+C) in U937 cells. Coexpression L+P+C led to synergistic response, whereas coexpression I kappa alpha/MAD-3 protein, place p65, blocked induction. series 5' deletion mutants promoter were used define two response regions: region located between -2800 -2720 bp II -512 -133 bp. Electrophoretic mobility shift assays confirmed B-like proteins could bind consensus binding sites II. site-specific mutation only one (-296/-286 bp) caused specific loss induction L+P+C. element (CRE) site (-2761/-2753 has been shown previously be critical for Mutation CRE an enhancerless test copies transactivation p65. Likewise, alpha inhibited CRE-dependent wild-type counterpart. These data regulates nonconsensus addition at -296/-286 suggest may play multiple roles transcription.