HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals

Daniel Bandarra, John Biddlestone, Sharon Mudie, H. -Arno J. Müller, Sonia Rocha (Lead / Corresponding author)

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    30 Citations (Scopus)

    Abstract

    Hypoxia and inflammation are intimately linked. It is known that nuclear factor κB (NF-κB) regulates the hypoxia-inducible factor (HIF) system, but little is known about how HIF regulates NF-κB. Here, we show that HIF-1α represses NF-κB-dependent gene expression. HIF-1α depletion results in increased NF-κB transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1α depletion enhances the NF-κB response, and this required not only the TAK-IKK complex, but also CDK6. Loss of HIF-1α results in an increased angiogenic response in mammalian cancer cells and increased mortality in Drosophila following infection. These results indicate that HIF-1α is required to restrain the NF-κB response, and thus prevents excessive and damaging proinflammatory responses.

    Original languageEnglish
    Pages (from-to)169-181
    Number of pages13
    JournalDisease Models & Mechanisms
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - Feb 2015

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    Keywords

    • Drosophila
    • HIF-1
    • Hypoxia
    • IKK
    • Inflammation
    • Nf-κb

    Cite this

    Bandarra, D., Biddlestone, J., Mudie, S., Müller, H. -A. J., & Rocha, S. (2015). HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Disease Models & Mechanisms, 8(2), 169-181. https://doi.org/10.1242/dmm.017285