Hypoxia activates IKK-NF-κB and the immune response in Drosophila melanogaster

Hypoxia, or low oxygen availability, is an important physiological and pathological stimulus for multicellular organisms. Molecularly, hypoxia activates a transcriptional programme directed at restoration of oxygen homoeostasis and cellular survival. In mammalian cells, hypoxia not only activates the HIF (hypoxia-inducible factor) family, but also additional transcription factors such as NF-kappa B (nuclear factor kappa B). Here we show that hypoxia activates the IKK-NF-kappa B [I kappa B (inhibitor of nuclear factor kappa B)-NF-kappa B] pathway and the immune response in Drosophila melanogaster. We show that NF-kappa B activation is required for organism survival in hypoxia. Finally, we identify a role for the tumour suppressor Cyld, as a negative regulator of NF-kappa B in response to hypoxia in Drosophila. The results indicate that hypoxia activation of the IKK-NF-kappa B pathway and the immune response is an important and evolutionary conserved response.