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Hepcidin Decreases Iron Transporter Expression in Vivo in Mouse Duodenum and Spleen and in Vitro in THP-1 Macrophages and Intestinal Caco-2 Cells

Chung, B; Chaston, T; Marks, J; Srai, SK; Sharp, PA; (2009) Hepcidin Decreases Iron Transporter Expression in Vivo in Mouse Duodenum and Spleen and in Vitro in THP-1 Macrophages and Intestinal Caco-2 Cells. J NUTR , 139 (8) 1457 - 1462. 10.3945/jn.108.102905.

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Abstract

Hepcidin is thought to control iron metabolism by interacting with the iron efflux transporter ferroportin. In macrophages, there is compelling evidence that hepcidin directly regulates ferroportin protein expression. However, the effects of hepcidin on intestinal ferroportin levels are less conclusive. In this study, we compared the effects of hepcidin on iron transporter expression in the spleen and duodenum of mice treated with hepcidin over a 24- to 72-h period and observed a marked decrease in the expression of ferroportin in both duodenal enterocytes and splenic macrophages following treatment. Changes in transporter protein expression were associated with significant decreases in duodenal iron transport and serum iron. In THP-1 macrophages, ferroportin protein levels were decreased by 300 and 1000 nmol/L hepcidin. In contrast, ferroportin protein expression was unaltered in intestinal Caco-2 cells following exposure to hepcidin. However, iron efflux from Caco-2 cells was significantly inhibited in the presence of hepcidin, suggesting that the peptide could block ferroportin function in these cells. We conclude that hepcidin regulates the release of iron from both enterocytes and macrophages. However, taken together with our previous work, it is apparent that macrophages are more sensitive than enterocytes to a hepcidin challenge. J. Nutr. 139 1457-1462, 2009.

Type: Article
Title: Hepcidin Decreases Iron Transporter Expression in Vivo in Mouse Duodenum and Spleen and in Vitro in THP-1 Macrophages and Intestinal Caco-2 Cells
DOI: 10.3945/jn.108.102905
Keywords: REGULATORY HORMONE HEPCIDIN, EPITHELIAL-CELLS, GENE-EXPRESSION, DOWN-REGULATION, ABSORPTION, FERROPORTIN, METABOLISM, HEMOCHROMATOSIS, MICE, PROTEINS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/168691
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