Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Theurl, M; Theurl, I; Hochegger, K; Obrist, P; Subramaniam, N; van Rooijen, N; Schuemann, K; Weiss, G.
Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression.
J Mol Med (Berl). 2008; 86(7):825-835
Doi: 10.1007/s00109-008-0346-y
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- Eller Kathrin
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antimicrobial Cationic Peptides - genetics Antimicrobial Cationic Peptides - metabolism
- Cell Line, Tumor -
- Gene Expression Regulation -
- Hepatocytes - metabolism
- Humans -
- Iron - metabolism
- Kupffer Cells - metabolism
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- RNA, Messenger - metabolism
- Find related publications in this database (Keywords)
- hepcidin
- hepatocytes
- Kupffer cells
- iron
- liposomes
- hemochromatosis