Blunted hepcidin response to inflammation in the absence of Hfe and transferrin receptor 2

Wallace, Daniel F., McDonald, Cameron J., Ostini, Lesa and Subramaniam, V. Nathan (2011) Blunted hepcidin response to inflammation in the absence of Hfe and transferrin receptor 2. Blood, 117 10: 2960-2966. doi:10.1182/blood-2010-08-303859


Author Wallace, Daniel F.
McDonald, Cameron J.
Ostini, Lesa
Subramaniam, V. Nathan
Title Blunted hepcidin response to inflammation in the absence of Hfe and transferrin receptor 2
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2011-03-10
Sub-type Article (original research)
DOI 10.1182/blood-2010-08-303859
Volume 117
Issue 10
Start page 2960
End page 2966
Total pages 7
Place of publication Washington, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
The induction of the iron-regulatory peptide hepcidin by proinflammatory cytokines is thought to result in the withholding of iron from invading pathogens. Hfe and transferrin receptor 2 (Tfr2) are involved in the homeostatic regulation of hepcidin and their disruption causes hereditary hemochromatosis (HH). To determine whether either Hfe or Tfr2 is involved in the inflammatory pathway regulating hepcidin, we analyzed the effect of inflammation in 3 mouse models of HH. The inflammatory response and indicators of iron homeostasis were measured in wild-type, Hfe−/−, Tfr2−/−, and Hfe−/−/Tfr2−/− mice injected with lipopolysaccharide (LPS). The administration of LPS significantly reduced serum iron in wild-type and Hfe−/− mice, with smaller reductions in Tfr2−/− and Hfe−/−/Tfr2−/− mice. Low basal levels of hepcidin in the Hfe−/−/Tfr2−/− mice were increased in response to LPS, but remained significantly lower than in the other strains of mice. These results suggest that despite the absence of Hfe and Tfr2, hepcidin is responsive to inflammation; however, the low basal expression and subsequent low levels of circulating hepcidin are insufficient to reduce serum iron effectively. This suggests that in HH, the iron-withholding response to invading pathogens may be inadequate, and this is especially the case in the absence of both Hfe and Tfr2.
Keyword Hereditary hemochromatosis
Vibrio-vulnificus
Iron homeostasis
Knockout mouse
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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