-
Views
-
Cite
Cite
Setsuko Mise-Omata, Etsushi Kuroda, Junko Niikura, Uki Yamashita, Yuichi Obata, Takahiro S Doi, A Proximal κB Site in the IL-23 p19 Promoter Is Responsible for RelA- and c-Rel-Dependent Transcription, The Journal of Immunology, Volume 179, Issue 10, November 2007, Pages 6596–6603, https://doi.org/10.4049/jimmunol.179.10.6596
Close - Share Icon Share
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.
