Central role of hypoxia inducible factor in the regulation of myeloid cell-mediated inflammation. Under conditions of reduced oxygenation, hydroxylase inhibition and the presence of bacteria/bacterial lipopolysaccharide (LPS), hypoxia inducible factor (HIF) is stabilized and modulates the expression of hypoxia response element (HRE)-responsive genes – resulting in the upregulation of myeloid cell glycolysis, microbicidal proteases, phagocytosis and vascular permeability, and consequently enhanced macrophage and neutrophil recruitment, bacterial killing and persistent myeloid cell-mediated inflammation. PHD, prolyl hydroxylase domain-containing enzyme; FIH, factor inhibiting HIF; IKKB, IκB kinase beta; SLC11a1, phagocyte-specific solute particle carrier 11A1 protein.
Walmsley et al. Arthritis Research & Therapy 2009 11:219 doi:10.1186/ar2632