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Hepcidin production in response to iron is controlled by monocyte-derived humoral factors.

Abstract
Hepcidin, which is mainly produced by the liver, is the key regulator in iron homeostasis. Hepcidin expression is up-regulated by iron loading in vivo, but the mechanism underlying this process is not completely understood. In the present study, we investigated the mechanism, following the hypothesis that hepcidin production in response to iron loading is regulated by extra-hepatic iron sensors. We measured serum hepcidin concentrations and iron indices in Wistar rats treated with saccharated ferric oxide (SFO). Human hepatoma-derived HepG2 cells were stimulated using SFO-administered rat sera, and co-cultured with rat spleen cells, human monocyte-derived THP-1 cells, or human monocytes with diferric transferrin (holo-Tf), and hepcidin concentrations in the conditioned media were measured. SFO elevated rat serum hepcidin concentrations. SFO-treated rat sera increased hepcidin production from HepG2 cells, and this induction correlated with serum hepcidin levels, but not with iron indices. Holo-Tf up-regulated hepcidin concentrations in media from HepG2 cells co-cultured with rat spleen cells, THP-1 cells, or human monocytes with or without cell-to-cell contacts, while holo-Tf did not up-regulate hepcidin from HepG2 cells alone. Our results suggest the existence of humoral factors capable of inducing hepcidin production that are secreted by extra-hepatic cells, such as reticuloendothelial monocytes, in response to iron.
AuthorsYusuke Sasaki, Yasushi Shimonaka, Katsuya Ikuta, Takaaki Hosoki, Katsunori Sasaki, Yoshihiro Torimoto, Hirotaka Kanada, Yoshiyuki Moriguchi, Yutaka Kohgo
JournalInternational journal of hematology (Int J Hematol) Vol. 99 Issue 1 Pg. 12-20 (Jan 2014) ISSN: 1865-3774 [Electronic] Japan
PMID24293278 (Publication Type: Journal Article)
Chemical References
  • Cytokines
  • Ferric Compounds
  • Hepcidins
  • Transferrin
  • holotransferrin
  • Iron
  • Ferric Oxide, Saccharated
  • Glucaric Acid
Topics
  • Animals
  • Cell Line
  • Coculture Techniques
  • Cytokines (blood, metabolism)
  • Ferric Compounds (administration & dosage, pharmacology)
  • Ferric Oxide, Saccharated
  • Glucaric Acid (administration & dosage, pharmacology)
  • Hep G2 Cells
  • Hepcidins (biosynthesis, blood)
  • Humans
  • Iron (metabolism, pharmacology)
  • Leukocytes, Mononuclear (drug effects, metabolism)
  • Male
  • Monocytes (drug effects, metabolism)
  • Rats
  • Spleen (cytology)
  • Transferrin (pharmacology)

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