The cellular response to hypoxia is coordinated by Hypoxia- inducible factor 1 (HIF-1). Oxygen-dependent regulation of the HIF-1a/b heterodimer depends on the abundance of the oxygen labile a-subunit which is posttranslationally stabilized under low oxygen tension. In addition, HIF-1 activation plays an important role in the inflammatory response where activation is achieved on multiple levels: Nitric oxide (NO) interferes with normoxic degradation of HIF-1a via proteasomes; inflammatory cytokines like IL-1b and TNF-a increase HIF-1a protein by enhancing the efficiency of HIF-1a mRNA translation; finally, bacterial lipopolysaccharides have recently been found to increase the expression and also the translation of HIF-1a mRNA in human monocytic cells. These different mechanisms cooperatively increase HIF-1a under normoxic conditions but, moreover, synergistically enhance hypoxic accumulation. In neutrophils which are responsible for the first line of defense against infections, HIF-1 is of critical importance for survival and energy homeostasis. Moreover, HIF-1 dependent gene expression also includes prolyl hydroxylases which act as cellular oxygen sensors. Thus, inflammatory mediators also affect oxygen sensing. HIF-1 activation in these inflammatory settings obviously relies on multiple mechanisms to ensure HIF-1 dependent gene expression both under hypoxia and normoxia. Supported DFG grants FA 225/18-19-20