A proximal kappa B site in the IL-23 p19 promoter is responsible for RelA- and c-rel-dependent transcription

作者：Mise Omata Setsuko; Kuroda Etsushi; Niikura Junko; Yamashita Uki; Obata Yuichi; Doi Takahiro S^*

来源：The Journal of Immunology, 2007, 179(10): 6596-6603.

IL-23 is a heterodimeric cytokine composed of a unique p19 subunit and a common p40 subunit is shared with IL-12. IL-23 promotes the inflammatory response by inducing the expansion of CD4(+) cells producing IL-17. The regulation of p19 gene expression has been less studied than that of p40 subunit expression, which in macrophages is well known to be dependent on NF-kappa B. To clarify the role of NF-kappa B in expression of the p19 gene, we analyzed mRNA levels in NF-kappa B-deficient macropbages. As reported to occur in dendritic cells, p19 expression was dramatically reduced in c-rel-deficient macrophages. Moreover, we found that p19 expression was halved in rela-deficient macrophages, but it was enhanced in p52-deficient macrophages. The p19 promoter contains three putative kappa B sites, located at nt -642 to -632 (kappa B-642), nt -513 to -503 (kappa B-513), and nt -105 to -96 (kappa B-105), between the transcription start site and -937 bp upstream in the p19 promoter region. Although EMSA analysis indicated that both kappa B-105 and kappa B-642, but not kappa B-513, bound to NF-kappa B in vitro, luciferase-based reporter assays showed that the most proximal kappa B site, kappa B-105, was uniquely indispensable to the induction of p19 transcription. Chromatin immuno-precipitation demonstrated in vivo association of RelA, c-Rel, and p50 with kappa B-105 of the p19 promoter. These results provide the evidence that the association of RelA and c-Rel with the proximal kappa B site in the p19 promoter is required to induce of p19 expression.

• 出版日期2007-11-15