RRC ID 28637
Author Mise-Omata S, Kuroda E, Niikura J, Yamashita U, Obata Y, Doi TS.
Title A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription.
Journal J Immunol
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-kappaB. To clarify the role of NF-kappaB in expression of the p19 gene, we analyzed mRNA levels in NF-kappaB-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 kappaB sites, located at nt -642 to -632 (kappaB-642), nt -513 to -503 (kappaB-513), and nt -105 to -96 (kappaB-105), between the transcription start site and -937 bp upstream in the p19 promoter region. Although EMSA analysis indicated that both kappaB-105 and kappaB-642, but not kappaB-513, bound to NF-kappaB in vitro, luciferase-based reporter assays showed that the most proximal kappaB site, kappaB-105, was uniquely indispensable to the induction of p19 transcription. Chromatin immunoprecipitation demonstrated in vivo association of RelA, c-Rel, and p50 with kappaB-105 of the p19 promoter. These results provide the evidence that the association of RelA and c-Rel with the proximal kappaB site in the p19 promoter is required to induce of p19 expression.
Volume 179(10)
Pages 6596-603
Published 2007-11-15
DOI 10.4049/jimmunol.179.10.6596
PII 179/10/6596
PMID 17982049
MeSH Animals Base Sequence CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism Gene Expression Regulation / physiology* Interleukin-12 Subunit p40 / biosynthesis Interleukin-12 Subunit p40 / genetics Interleukin-12 Subunit p40 / immunology Interleukin-17 / biosynthesis Interleukin-17 / genetics Interleukin-17 / immunology Interleukin-23 Subunit p19 / biosynthesis* Interleukin-23 Subunit p19 / genetics Interleukin-23 Subunit p19 / immunology Macrophages / immunology Macrophages / metabolism Mice Mice, Knockout Molecular Sequence Data NF-kappa B / genetics NF-kappa B / immunology NF-kappa B / metabolism* Protein Binding Proto-Oncogene Proteins c-rel / genetics Proto-Oncogene Proteins c-rel / immunology Proto-Oncogene Proteins c-rel / metabolism* Response Elements / physiology* Transcription Factor RelA / genetics Transcription Factor RelA / immunology Transcription Factor RelA / metabolism* Transcription, Genetic / physiology*
IF 4.886
Times Cited 71
DNA material p19-937-Luc (RDB06302) p19-685-Luc (RDB06303) p19-584-Luc (RDB06304) p19-484-Luc (RDB06305) p19-184-Luc (RDB06307) p19-83-Luc (RDB06308) p19-937 mkB-105-Luc (RDB06309) p19-937 mkB-642-Luc (RDB06310) p19-937 mkB-642 mkB-105-Luc (RDB06311) p19-584 mkB-513-Luc (RDB06312) p19-584 mkB-105-Luc (RDB06313) p19-184 mkB-105-Luc (RDB06314) p19-154-Luc (RDB06315)
Mice RBRC00300
Human and Animal Cells RAW 264(RCB0535) J774.1(RCB0434)