Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression

Theurl, Milan, Theurl, Igor, Hochegger, Kathrin, Obrist, Peter, Subramaniam, Nathan, van Rooijen, Nico, Schuemann, Klaus and Weiss, Guenter (2008) Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression. Journal of Molecular Medicine, 86 7: 825-835. doi:10.1007/s00109-008-0346-y


Author Theurl, Milan
Theurl, Igor
Hochegger, Kathrin
Obrist, Peter
Subramaniam, Nathan
van Rooijen, Nico
Schuemann, Klaus
Weiss, Guenter
Title Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression
Journal name Journal of Molecular Medicine   Check publisher's open access policy
ISSN 0946-2716
Publication date 2008-06-25
Year available 2008
Sub-type Article (original research)
DOI 10.1007/s00109-008-0346-y
Open Access Status
Volume 86
Issue 7
Start page 825
End page 835
Total pages 11
Editor D. Gantenm
F. McCormick
Place of publication Germany
Publisher Springer
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
060104 Cell Metabolism
Abstract Hepcidin, a small cationic liver derived peptide, is a master regulator of body iron homeostasis. Cytokines and iron availability have so far been identified as regulators of hepcidin expression. Herein, we investigated the functional role of Kupffer cells for hepcidin expression because of their vicinity to the hepatocytes and their importance for iron recycling via erythrophagocytosis. We investigated C57Bl6 mice and littermates, in which Kupffer cells were eliminated in vivo upon intravenous injection of liposome-encapsulated clodronate. Primary cultures of hepatocytes and Kupffer cells were used to study direct regulatory effects ex vivo. The in vivo depletion of Kupffer cells resulted in a significant increase in liver hepcidin expression, which was paralleled by a significant reduction in serum iron levels. The same pattern of regulation by Kupffer cell depletion was observed upon injection of bacterial lipopolysaccharide into mice and in primary (Hfe −/−) and in secondary iron-overloaded mice. Accordingly, the messenger ribonucleic acid (mRNA) concentrations of the hepcidin iron-sensing molecule hemojuvelin were not significantly changed upon Kupffer cell depletion. When primary hepatocytes were cocultivated with Kupffer cells or stimulated with a Kupffer cell-conditioned medium ex vivo, a significant reduction in hepatocyte hepcidin mRNA expression was observed. Our data suggest that Kupffer cells control body iron homeostasis by exerting negative regulatory signals toward hepcidin expression, which may be primarily referred to the secretion of yet unidentified hepcidin-suppressing molecules by Kupffer cells.
Keyword Hepcidin
Hepatocytes
Kupffer
cells
Iron
Liposomes
Hemochromatosis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 08 Apr 2009, 01:01:18 EST by Amanda Jones on behalf of Faculty Of Health Sciences