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)

    Research output: Contribution to journalArticlepeer-review

    91 Citations (Scopus)


    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 and Mechanisms (DMM)
    Issue number2
    Publication statusPublished - Feb 2015


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

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine (miscellaneous)
    • Immunology and Microbiology (miscellaneous)
    • Neuroscience (miscellaneous)


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