Hepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1 monocytes.
OBJECTIVE
The antimicrobial peptide hepcidin is generated in the liver and released into the circulation in response to iron, oxygen and inflammatory signals. Hepcidin serves as a hormonal regulator of duodenal iron absorption and iron trafficking in the reticuloendothelial system. The aim of this study is to explore the effects of this regulatory peptide in macrophage iron metabolism.


METHODS
Hepcidin-mediated iron efflux and parameters of cellular iron homeostasis were studied in THP1 monocytic cells co-cultured with hepcidin-producing hepatic cells.


RESULTS
Stimulation of hepcidin expression in Huh7 cells with interleukin-6 promoted a significant approximately 30% decrease in 59Fe efflux from THP1 cells, previously loaded with 59Fe-transferrin. Similar results were obtained with HepG2 cells transfected with a hepcidin cDNA. Importantly, hepcidin expression from Huh7 cells elicited a decrease in the levels of the iron-sensitive post-transcriptional regulator IRP2 in THP1 cells, accompanied by de novo synthesis of the iron storage protein ferritin.


CONCLUSIONS
Physiologically generated hepcidin inhibits iron efflux and promotes iron accumulation in monocytic cells, mimicking a pathophysiological response commonly observed in the anemia of inflammation. Our results highlight the crucial role of hepcidin in the control of macrophage iron homeostasis.
Andriopoulos
Bill
B
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Road, and Department of Medicine, McGill University, Montreal, Que., Canada H3T 1E2.
Pantopoulos
Kostas
K
D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018076:DNA, Complementary / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D014162:Transfection
D023181:Antimicrobial Cationic Peptides; D018076:DNA, Complementary; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D007501:Iron