Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations.
The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hepcidin expression, have led many to consider it the major mediator of ACD. However, if hepcidin is the major factor responsible for ACD, then it should also contribute to the impaired erythropoiesis observed in this syndrome. Erythroid colony formation in vitro was inhibited by hepcidin at erythropoietin (Epo) concentrations less than or equal to 0.5 U/mL but not at Epo 1.0 U/mL. At Epo concentrations of 0.3 U/mL, HCD57 erythroleukemia cells exposed to hepcidin exhibit decreased expression of the antiapoptotic protein pBad compared with controls. These studies suggest that hepcidin may contribute to anemia in ACD not only through effects on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival.
Dallalio
Gail
G
Medical Service (111), VA Medical Center Rm A 429, 1101 Veterans Dr, Lexington, KY. robert.means@uky.edu.
Law
Erin
E
Means
Robert T
RT
D000740:Anemia / Q000097:blood / Q000209:etiology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002908:Chronic Disease; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000502:physiology*; D064451:Hepcidins; D006801:Humans
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D004921:Erythropoietin