Hypoxia Regulation of NF kappa B signalling during inflammation: the role of hydroxylases

NF kappa B is a master regulator of innate immunity and inflammatory signalling. Microenvironmental hypoxia has long been identified as being coincident with chronic inflammation. The contribution of microenvironmental hypoxia to NF kappa B-induced inflammation has more recently been appreciated. Identification of the co-regulation of NF kappa B and hypoxia inducible factor (HIF) pathways by 2-oxoglutarate-dependent hydroxylase family members has highlighted an intimate relationship between NF kappa B inflammatory signalling and HIF-mediated hypoxic signalling pathways. Adding another layer of complexity to our understanding of the role of NF kappa B inflammatory signalling by hypoxia is the recent recognition of the contribution of basal NF kappa B activity to HIF-1 alpha transcription. This observation implicates an important and previously unappreciated role for NF kappa B in inflammatory disease where HIF-1 alpha is activated. The present review will discuss recent literature pertaining to the regulation of NF kappa B inflammatory signalling by hypoxia and some of the inflammatory diseases where this may play an important role. Furthermore, we will discuss the potential for prolyl-hydroxylase inhibitors in inflammatory disease.