3/11/22, 6:41 AM Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells | Gut

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Hepatology

Evidence for differential effects of hepcidin in macrophages PDF

and intestinal epithelial cells
T Chaston 1 , B Chung 1 , M Mascarenhas 1 , 2 , J Marks 2 , B Patel 2 , S K Srai 2 , P Sharp 1
Dr Paul Sharp, Department of Nutrition & Dietetics, King’s College London, Franklin–Wilkins Building, 150
Stamford Street, London, SE1 9NH, UK; paul.a.sharp@kcl.ac.uk

Abstract
Background and aims: Reticulo-endothelial macrophages together with duodenal enterocytes
coordinate body iron homeostasis. The aim of this study was to investigate the regulatory actions of the
hormone hepcidin on ferroportin expression in these two cell types.

Methods: We investigated the in vitro effects of hepcidin in well-characterised human cell culture models
of macrophages (differentiated THP-1 cells) and intestinal epithelial cells (Caco-2 cells). The in vivo
effects of hepcidin were also investigated in mice injected with a synthetic hepcidin peptide.

Results: Exposure to hepcidin (presented either as conditioned medium from interleukin-6-stimulated

HuH7 cells or as a synthetic peptide) resulted in a rapid (within 4 h) decrease in ferroportin expression in
THP-1 macrophages but had no effect on ferroportin levels in Caco-2 cells. To determine whether these
rapid effects of hepcidin were also evident in vivo we injected mice with a synthetic hepcidin peptide.
Four hours post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were
decreased significantly and the hepcidin-treated mice developed hypoferraemia. Interestingly, in the
same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron
transport.

Conclusions: These data suggests that the rapid response to hepcidin is cell type and tissue specific.
Upon its release, hepcidin initially targets macrophage iron recycling. The duodenum appears to be less
sensitive to this initial rise in hepcidin levels. We believe the fact that macrophages respond more acutely
to a hepcidin challenge is fully consistent with their central role in maintaining body iron homeostasis.

http://dx.doi.org/10.1136/gut.2007.131722

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3/11/22, 6:41 AM Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells | Gut

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Footnotes

Competing interests: None

Funding: This work was funded by grants from the Biotechnology and Biological Sciences Research
Council and the University of London Central Research Fund. Bomee Chung is part funded by the
Overseas Research Student (ORS) Award Scheme.

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Copyright information: 2008 BMJ Publishing Group and British Society of Gastroenterology

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