Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse lipopolysaccharide-induced inflammation in HFE-deficient and wild types


ABSTRACT: Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is the anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron storage, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this “iron withholding” reduces the iron available to developing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp has antimicrobial activity and is part of the type II acute phase response. It is also thought to play a critical regulatory role in the sequestration of iron in the context of ACD. We report that mice with deficiencies in the hemochromatosis gene product, Hfe, mount a general inflammatory response, but lack appropriate Hamp expression and fail to develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD.

ORGANISM(S): Mus musculus

DISEASE(S): murine hemochromatosis

SUBMITTER: Cindy Roy 

PROVIDER: E-MEXP-95 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice.

Roy Cindy N CN   Custodio Angel O AO   de Graaf Jos J   Schneider Susanne S   Akpan Imo I   Montross Lynne K LK   Sanchez Mayka M   Gaudino Alessandro A   Hentze Matthias W MW   Andrews Nancy C NC   Muckenthaler Martina U MU  

Nature genetics 20040418 5


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 event  ...[more]

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