[Synergism between transcription factors NF-IL6 and NF-kappa B in IL-6 gene regulation].
NF-IL6 and NF-kappa B are nuclear proteins supposed to play an important role in the regulation of acute-phase protein synthesis and inflammatory response against infection and tissue injury as a host defence mechanism. In addition the promoter region of the interleukin-6 (IL-6) gene has a NF-kappa B binding motif as well as a NF-IL6 binding site. Considering of these facts, we come to investigate that there may be a synergistic effect between NF-IL6 and NF-kappa B in the regulation of IL-6 gene expression. In order to study it, some combinations of expression vectors NF-IL6 cDNA, NF-kappa B (p50/p65) cDNA and reporter plasmid K18-CAT which contains human IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) gene, were transfected into Jurkat cells and the CAT activities were examined. Co-transfection of NF-IL6 and NF-kappa B (p50/p65) cDNA revealed a dramatic increase of acetylated [14C] chloramphenicol, and its CAT activity reached to 40%. Then, co-transfection of NF-IL6 and NF-kappa B subunit p65 alone showed a high level of CAT activity, too. When 5' deletion mutant reporter plasmid K9-CAT lacking the NF-IL6 binding site was used, co-transfection of NF-IL6 and NF-kappa B (p50/p65) showed low level of CAT activity. These results indicate that there is a synergistic effect between NF-IL6 and NF-kappa B (p50/p65) in IL-6 gene regulation. Among two subunits of NF-kappa B (p50/p65), p65 seems to play an important role rather than p50 does in synergism between NF-IL6 and NF-kappa B. Besides, this synergistic function comes to work only when NF-IL6 binds to its binding site of IL-6 promoter region.
Fujikawa
K
K
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase