Hepcidin--a peptide hormone at the interface of innate immunity and iron metabolism.
Hepcidin is a cationic amphipathic peptide made in the liver, released into plasma and excreted in urine. Hepcidin is the homeostatic regulator of intestinal iron absorption, iron recycling by macrophages, and iron mobilization from hepatic stores, but it is also markedly induced during infections and inflammation. Under the influence of hepcidin, macrophages, hepatocytes, and enterocytes retain iron that would otherwise be released into plasma. Hepcidin acts by inhibiting the efflux of iron through ferroportin, the sole known iron exporter that is expressed in the small intestine, and in hepatocytes and macrophages. As befits an iron-regulatory hormone, hepcidin synthesis is increased by iron loading, and decreased by anemia and hypoxia. Hepcidin is also rapidly induced by cytokines, including IL-6. The resulting decrease in plasma iron levels eventually limits iron availability to erythropoiesis and contributes to the anemia associated with infection and inflammation. The decrease in extracellular iron concentrations due to hepcidin probably limits iron availability to invading microorganisms, thus contributing to host defense.
Ganz
T
T
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles 90095-1690, USA. tganz@mednet.ucla.edu
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000502:physiology*; D006432:Hemochromatosis / Q000151:congenital / Q000276:immunology; D064451:Hepcidins; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D007501:Iron