Hypoxia is associated with a diverse range of physiological and pathophysiological processes, including development, wound healing,
inflammation,
vascular disease and
cancer. The requirement that eukaryotic cells have for molecular
oxygen as the terminal electron acceptor for the electron transport chain means that the maintenance of
oxygen delivery is key for bioenergetic homeostasis. Metazoans have evolved an effective way to adapt to hypoxic stress at the molecular level through a
transcription factor termed the
hypoxia inducible factor. A family of
oxygen-sensing
hydroxylases utilizes molecular
oxygen as a co-substrate for the hydroxylation of
hypoxia inducible factor α subunits, thereby reducing its expression and transcriptional activity when
oxygen is available. Recent studies have indicated that other
hypoxia-responsive transcriptional pathways may also be
hydroxylase-dependent. In this review, we will discuss the role of
hydroxylases in the regulation of NF-κB, a key regulator of immunity and
inflammation. Developing our understanding of the role of
hydroxylases in hypoxic
inflammation may identify novel therapeutic approaches in chronic inflammatory disease.