Article Text

other Versions

PDF
Evidence For Differential Effects Of Hepcidin In Macrophages And Intestinal Epithelial Cells.
  1. Timothy Chaston
  1. King's College London, United Kingdom
    1. Bomee Chung
    1. King's College London, United Kingdom
      1. Monica Mascarenhas
      1. University College London, United Kingdom
        1. Joanne Marks
        1. University College London, United Kingdom
          1. Bhavini Patel
          1. University College London, United Kingdom
            1. Surjit Kaila Srai
            1. University College London, United Kingdom
              1. Paul Sharp (paul.a.sharp{at}kcl.ac.uk)
              1. King's College London, United Kingdom

                Abstract

                Background and aims: Reticuloendothelial macrophages together with duodenal enterocytes co-ordinate 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-characterized 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. 4 h post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were decreased significantly and the hepcidin-treated mice developed hypoferremia. Interestingly, in the same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron transport. Conclusions: These data suggest 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.

                • duodenum
                • ferroportin
                • hepcidin
                • iron
                • spleen

                Statistics from Altmetric.com

                Request permissions

                If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

                Linked Articles

                • Digest
                  Robin Spiller Magnus Simren