Journal article
Hemochromatosis Protein (HFE) and Tumor Necrosis Factor Receptor 2 (TNFR2) Influence Tissue Iron Levels: Elements of a Common Gut Pathway?
Blood cells, molecules, & diseases, Vol.29(3), pp.274-285
11/01/2002
DOI: 10.1006/bcmd.2002.0565
PMID: 12547217
Abstract
ABSTRACT
Quantitative genetic analysis of hepatic and splenic iron levels in recombinant inbred mice yielded a quantitative trait locus that was found to coincide with the genomic locale encompassing the tumor necrosis factor receptor 2 gene (
Tnfr2). When fed an iron-enriched diet, mice nullizygous with respect to
Tnfr2, but not the
Tnfr1 gene, showed a significant increase in splenic non-heme iron levels. This result contrasted with mice deficient in the hemochromatosis protein, HFE, which demonstrated a significant increase in normally high hepatic iron levels, but no change in splenic iron, when fed an iron-enriched chow. Both
Tnfr2 knockout and
HFE knockout mice fed an iron-enriched diet failed to demonstrate intestinal epithelial cell iron following the application of the Perls' stain, as compared to both
Tnfr1 knockout and normal control mice. Moreover, intestinal intraepithelial lymphocytes (IELs) isolated from HFE knockout mice did not show an increase in TNF expression following challenge with the iron-enriched diet, in contrast to normal controls. These results suggest that HFE and TNFR2 are both involved in regulating iron deposition in tissues and that the regulation occurs at the level of the intestine through IEL-orchestrated production of TNF following the binding to TNFR2. These data suggest that HFE and TNFR2 may contribute to a common pathway of the iron stores regulator insuring the controlled efflux of gut iron.
Details
- Title: Subtitle
- Hemochromatosis Protein (HFE) and Tumor Necrosis Factor Receptor 2 (TNFR2) Influence Tissue Iron Levels: Elements of a Common Gut Pathway?
- Creators
- Paul N. Meyer - Pennsylvania State UniversityGlenn S. Gerhard - Department of Pathology, Dartmouth Medical School, Hanover, NHYukinori Yoshida - Pennsylvania State UniversityMika Yoshida - Pennsylvania State UniversityKaren A. Chorney - Pennsylvania State UniversityJohn Beard - Pennsylvania State UniversityElizabeth J. Kauffman - Pennsylvania State UniversityGünter Weiss - University Hospital InnsbruckMichael J. Chorney - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- Blood cells, molecules, & diseases, Vol.29(3), pp.274-285
- Publisher
- Elsevier Inc
- DOI
- 10.1006/bcmd.2002.0565
- PMID
- 12547217
- ISSN
- 1079-9796
- eISSN
- 1096-0961
- Number of pages
- 12
- Language
- English
- Date published
- 11/01/2002
- Academic Unit
- Pathology
- Record Identifier
- 9984823100902771
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