HIF-1α, a novel piece in the NF-κB puzzle

Abstract

Hypoxia, or low oxygen availability, is an important physiological stimulus for multicellular organisms. Molecularly, hypoxia induces a transcriptional programme directed at restoration of oxygen homeostasis and cellular survival. Hypoxia and inflammation are intimately linked, and even though it is known that NF-kB regulates the HIF system, little is known about how HIF regulates NF-kB. In a recent report we have shown that HIF-1a plays an important role in regulating NF-kB. Importantly, HIF-1a acted to restrict NF-kB transcriptional activity, in mammalian cells and in the in vivo genetic model of Drosophil a. Depletion of HIF-1a resulted in increased levels of specific NF-kB targets, by a mechanism dependent on TAK/IKK and CDK6. Deletion of the HIF-1a homologue in Drosophila , Sima, resulted in hypersensitivity to infection due to deregulated NF-kB. This report delineated for the first time the contribution of HIF-1a towards the NF-kB pathway, and demonstrated the importance of HIF-1a presence for the control of the inflammatory response in vivo . The importance of this crosstalk between HIF and NF-kB is significant, as it could create potential new therapies in diseases where hypoxia and inflammatory are prevalent.