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IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.
These studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL- 6-hepcid in axis is responsible for the hypoferremia of inflammation.
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
It is reported that hepcidin bound to ferroportin in tissue culture cells, leading to decreased export of cellular iron and the posttranslational regulation of ferroports by hePCidin may complete a homeostatic loop.
Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein.
- E. Nemeth, E. Valore, M. Territo, G. Schiller, A. Lichtenstein, T. Ganz
- Biology, MedicineBlood
- 1 April 2003
The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.
IDENTIFICATION OF ERYTHROFERRONE AS AN ERYTHROID REGULATOR OF IRON METABOLISM
- L. Kautz, G. Jung, E. Valore, S. Rivella, E. Nemeth, T. Ganz
- Medicine, BiologyNature Genetics
- 31 May 2014
A new hormone, erythroferrone (ERFE), is identified that mediates hepcidin suppression during stress erythropoiesis, and is greatly increased in Hbbth3/+ mice with thalassemia intermedia, where it contributes to the suppression of hePCidin and the systemic iron overload characteristic of this disease.
Hepcidin and iron homeostasis.
Mutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
The positional cloning of the locus associated with juvenile hemochromatosis is reported and the identification of a new gene crucial to iron metabolism is identified, now called HFE2, whose protein product the authors call hemojuvelin.
Regulation of iron metabolism by hepcidin.
The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
Immunoassay for human serum hepcidin.
The first serum enzyme-linked immunosorbent assay for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure, yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the etiology of iron disorders.
Hepcidin and disorders of iron metabolism.
The hepcidin-ferroportin axis is the principal regulator of extracellular iron homeostasis in health and disease, and is a promising target for the diagnosis and treatment of iron disorders and anemias.
Iron homeostasis in host defence and inflammation
Recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection are reviewed, emphasizing aspects that are applicable to human health and disease.