Inflammation and ER Stress Downregulate BDH2 Expression and Dysregulate Intracellular Iron in Macrophages

Figure 9

Schematic presentation of BDH2 downregulation in macrophages. BDH2 is the rate-limiting enzyme in the synthesis of the mammalian siderophore 2,5DHBA that detoxifies and traffics intracellular labile iron. Treatment of THP-1 macrophage-like monocytes with LPS or tunicamycin downregulates BDH2 expression leading to intracellular labile iron accumulation. Hepcidin is the master iron regulating hormone that binds to the only iron exporter ferroportin causing its internalization and degradation consequently preventing iron egress from macrophages. LPS and tunicamycin treatment increases hepcidin expression and downregulates ferroportin causing iron retention in macrophages. The downregulation of BDH2 contributes to altered cellular iron homeostasis.