title: The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes.
abstract: Chronic kidney disease affects 40% of adults aged 65 and older. Anemia of CKD is present in 30% of patients with CKD and is associated with increased cardiovascular risk, decreased quality of life, and increased mortality. Hepcidin-25 (hepcidin), the key iron regulating hormone, prevents iron egress from macrophages and thus prevents normal recycling of the iron needed to support erythropoiesis. Hepcidin levels are increased in adults and children with CKD. Vitamin D insufficiency is highly prevalent in CKD and is associated with erythropoietin hyporesponsiveness. Recently, hepcidin levels were found to be inversely correlated with vitamin D status in CKD. The aim of this study was to investigate the role of vitamin D in the regulation of hepcidin expressionin vitroandin vivo. This study reports that 1,25-dihydroxyvitamin D3(1,25(OH)2D3), the hormonally active form of vitamin D, is associated with decreased hepcidin and increased ferroportin expression in lipopolysaccharide (LPS) stimulated THP-1 cells. 1,25(OH)2D3also resulted in a dose-dependent decrease in pro-hepcidin cytokines, IL-6 and IL-1β, releasein vitro. Further, we show that high-dose vitamin D therapy impacts systemic hepcidin levels in subjects with early stage CKD. These data suggest that improvement in vitamin D status is associated with lower systemic concentrations of hepcidin in subjects with CKD. In conclusion, vitamin D regulates the hepcidin-ferroportin axis in macrophages which may facilitate iron egress. Improvement in vitamin D status in patients with CKD may reduce systemic hepcidin levels and may ameliorate anemia of CKD.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA ; Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
authors.forename: Susu M
authors.initials: SM
authors.lastname: Zughaier
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Alvarez
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sloan
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Konrad
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA ; Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
keywords: Anemia of inflammation; Chronic kidney disease; Ferroportin; Hepcidin; IL-1β; IL-6; Macrophage; NRAMP1; Vitamin D
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