title: Role of hepcidin in the setting of hypoferremia during acute inflammation.
abstract: The anemia of chronic disease (also called anemia of inflammation) is an acquired disorder of iron homeostasis associated with infection, malignancy, organ failure, trauma, or other causes of inflammation. It is now widely accepted that induction of hepcidin expression in response to inflammation might explain the characteristic hypoferremia associated with this condition. To determine the role of hepcidin in acute inflammation and the regulation of its receptor, the iron exporter, ferroportin, wild-type, heterozygote and hepcidin knockout mice (Hepc-/-) were challenged with sublethal doses of lipopolysaccharide (LPS). Six hours after injection, ferroportin mRNA and protein levels were assessed in the duodenum and the spleen and plasma iron was determined. Our results demonstrate that hepcidin is crucial, though not the sole mediator of LPS-mediated acute hypoferremia, and also that hepcidin major contribution relies on decreased ferroportin protein levels found in the spleen. Furthermore, we establish that LPS-mediated repression of the membrane iron transporter DMT1 and oxidoreductase Dcytb in the duodenum is independent of hepcidin. Finally, our results in the hepc+/- mice indicate that elevated hepcidin gene expression is not a prerequisite for the setting of hypoferremia during early inflammatory response, and they highlight the intimate crosstalk between inflammatory and iron-responsive pathways for the control of hepcidin.
authors: Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Faculté de Médecine Cochin Port Royal, Paris, France.
authors: Jean-Christophe
authors: JC
authors: Deschemin
authors: Sophie
authors: S
authors: Vaulont
mesh_terms: D000208:Acute Disease; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D064451:Hepcidins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007501:Iron / Q000097:blood*; D000090463:Iron Deficiencies; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D008070:Lipopolysaccharides; D000098742:Ferroportin; D007501:Iron
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