The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes

• Type of Material: Article
• Authors: Susu M Zughaier, Emory University; Jessica A. Alvarez, Emory University; John H. Sloan, Eli Lilly and Company; Robert J. Konrad, Eli Lilly and Company; Vin Tangpricha, Emory University
• Language: English
• Date: 2014-01-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jcte.2014.01.003
• Title of Journal or Parent Work: Journal of Clinical and Translational Endocrinology
• ISSN: 2214-6237
• Volume: 1
• Issue: 1
• Start Page: 19
• End Page: 25
• Grant/Funding Information: This work is supported in part by grants from Emory-Egleston Children's Research Center and Center for Pediatric Nanomedicine of Emory + Children's Pediatrics Research Center to S.M.Z, and by T32 DK007298-32S1 to J.A.A. S.M.Z. especially acknowledges the support of N. McCarty (Center for Cystic Fibrosis Research, Emory University School of Medicine) for providing the research facility and laboratory space where part of this work was conducted.
• Keywords: Hepcidin; Macrophage; Ferroportin; NRAMP1; Anemia of inflammation; IL-6; IL-1β; Vitamin D; Chronic kidney disease
• Research Categories: Health Sciences, General; Health Sciences, Immunology

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 expression in vitro and in vivo. This study reports that 1,25- dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 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) 2 D 3 also resulted in a dose-dependent decrease in pro-hepcidin cytokines, IL-6 and IL-1β, release in 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.