Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages

Xiao Bing Liu, Ngoc Bich H. Nguyen, Kimberly D. Marquess, Funmei Yang, David J. Haile

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Acute and chronic inflammatory states are associated with many changes in intracellular iron metabolism including sequestration of iron in the mononuclear-phagocyte system (MPS) and a decline in serum iron. Previous work in rodent models of acute inflammation has demonstrated inflammation-induced downregulation of intestinal and MPS iron exporter, ferroportin 1, mRNA and protein. In addition, these models have also demonstrated hepatic induction of mRNA of the small 25 amino acid peptide hepcidin. Hepcidin has been hypothesized to be the mediator of iron- and inflammation-induced changes in iron metabolism. The molecular details of the connection between iron metabolism, hepcidin and inflammation have become clearer with the recent finding of hepcidin-induced internalization and degradation of FPN1. The work presented here demonstrates that the lipopolysaccharide-induced splenic macrophage FPN1 mRNA downregulation is not dependent upon the action of a single cytokine such as IL-6, IL-1 or TNF-α because mice deficient in these pathways downregulate FPN1 normally. Furthermore, hepcidin is also synthesized in the spleen of normal mice and induced by lipopolysaccharide. Additionally, in vitro, splenic adherent cells produce hepcidin in response to lipopolysaccharide in an IL-6-dependent manner. There appear to be both probable transcriptional and post-transcriptional control of FPN1 expression by lipopolysaccharide-induced inflammation. The former effect is on mRNA expression and is independent of hepcidin, whereas the latter is IL-6- and hepcidin-dependent.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalBlood Cells, Molecules, and Diseases
Volume35
Issue number1
DOIs
StatePublished - Jul 1 2005

Keywords

  • Ferroportin
  • Hepcidin
  • Lipopolysaccharide
  • Splenic macrophage

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

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