Figure 2.

NFκB and hypoxia inducible factor 1 alpha cross-talk. Hypoxia acts as a stimulus for the activation of the inhibitor of κB kinase (IKK) complex as shown in Figure 1. Basal IKKβ-dependent NFκB activity is required for transcriptionally active dimer complexes to translocate to the nucleus and bind to a region -197/188 base pairs upstream of the hypoxia inducible factor (HIF)-1α promoter. This results in an increase in HIF-1α mRNA and protein levels. Several NFκB proteins have been detected at the HIF-1α promoter region by chromatin immunoprecipitation. Increased levels of HIF-1α are observed in chronically inflamed tissue such as the rheumatoid arthritis (RA) synovium and in the dermal glands of psoriatic skin. FIH, factor-inhibiting hypoxia inducible factor.