An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice
Author
Roy, Cindy N.
Custodio, Angel O.
de Graaf, Jos
Schneider, Susanne
Akpan, Imo
Montross, Lynne K.
Sanchez, Mayka
Gaudino, Alessandro
Hentze, Matthias W.
Andrews, Nancy C.
Muckenthaler, Martina U.
Publication date
2004ISSN
1061-4036
Abstract
Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia1. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone2,3 that inhibits duodenal iron absorption and macrophage iron release4,5,6,7. Hamp is part of the type II acute phase response8 and is thought to have a crucial regulatory role in sequestering iron in the context of ACD7,9. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Medicina
Medicina
Medicine
Pages
5
Publisher
Springer Nature
Collection
36
Is part of
Nature Genetics
Citation
Roy, Cindy N.; Custodio, Angel O.; de Graaf, Jos [et al.]. An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice. Nature Genetics, 2004, 36, p. 481–485. Disponible en: <https://www.nature.com/articles/ng1350>. Fecha de acceso: 22 ene. 2024. DOI: 10.1038/ng1350
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- Ciències de la Salut [725]