A proximal κB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription

Setsuko Mise-Omata, Etsushi Kuroda, Junko Niikura, Uki Yamashita, Yuichi Obata, Takahiro S. Doi

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70 Citations (Scopus)

Abstract

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-κB. To clarify the role of NF-κB in expression of the p19 gene, we analyzed mRNA levels in NF-κB-deficient macrophages. 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 κB sites, located at nt -642 to -632 (κB-642), nt -513 to -503 (κB-513), and nt -105 to -96 (κB-105), between the transcription start site and -937 bp upstream in the p19 promoter region. Although EMSA analysis indicated that both κB-105 and κB-642, but not κB-513, bound to NF-κB in vitro, luciferase-based reporter assays showed that the most proximal κB site, κB-105, was uniquely indispensable to the induction of p19 transcription. Chromatin immunoprecipitation demonstrated in vivo association of RelA, c-Rel, and p50 with κB-105 of the p19 promoter. These results provide the evidence that the association of RelA and c-Rel with the proximal κB site in the p19 promoter is required to induce of p19 expression.

Original languageEnglish
Pages (from-to)6596-6603
Number of pages8
JournalJournal of Immunology
Volume179
Issue number10
Publication statusPublished - 2007 Nov 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mise-Omata, S., Kuroda, E., Niikura, J., Yamashita, U., Obata, Y., & Doi, T. S. (2007). A proximal κB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription. Journal of Immunology, 179(10), 6596-6603.