Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter.

Academic Article

Abstract

  • IL-12 is a heterodimer composed of p40 and p35 and is a key cytokine that functions to protect the host from viral and microbial infections. IL-12 links the innate immune system with the acquired immune system during infection, and induces differentiation of type 1 T cells that play an important role in the eradication of microbes. The induction of the IL-12 p40 gene is regulated by NF-kappaB in the presence of IFN-gamma. IFN-gamma induces IFN regulatory factor-1 (IRF-1), which in turn induces the transcription of the IL-12 p40 gene. However, the IRF-1 binding site in the promoter region of the IL-12 p40 gene has not yet been formally determined. In the present study, we demonstrated that IRF-1 directly binds to the IL-12 p40 gene promoter and identified its binding site. The IRF-1 binding site in the promoter region of the IL-12 p40 gene is shown to be in the -72 to -58 area of the 5'-upstream region. The -63 to -61 position is the critical site within this region for the binding of IRF-1 to the IL-12 p40 gene promoter. While IFN-gamma must be present for IL-12 p40 gene induction, the p35 gene is strongly induced by LPS, even in the absence of IFN-gamma, and therefore the induction of the p35 gene is IRF-1 independent.

    • Authors

    Published In

    Keywords

  • 5' Untranslated Regions, Animals, Base Sequence, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Interferon Regulatory Factor-1, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit, Interferon-gamma, Interleukin-12, Interleukin-12 Subunit p35, Interleukin-12 Subunit p40, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Phosphoproteins, Promoter Regions, Genetic, Protein Binding, Protein Subunits, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Up-Regulation

    • Digital Object Identifier (doi)

    Pubmed Id

  • 22137656

    • Author List

  • Maruyama S; Sumita K; Shen H; Kanoh M; Xu X; Sato M; Matsumoto M; Shinomiya H; Asano Y

    • Start Page

  • 997

    • End Page

  • 1001

    • Volume

  • 170

    • Issue

  • 2