Modulation of hepcidin expression by normal control and beta0-thalassemia/Hb E erythroblasts

<p><b>Objectives:</b> The inherited genetic disorder beta0-thalassemia/Hb E disease is associated with the over-suppression of the master regulator of iron homeostasis, the peptide hormone hepcidin. How developing erythroid cells mediate the suppression of hepcidin remains controversial, although a number of inhibitors have been proposed.</p> <p><b>Methods:</b> To investigate the ability of erythroid cells to suppress hepcidin expression in liver cells, conditioned media from the culture of <i>in vitro</i> differentiating erythroblasts (from normal controls and beta0-thalassemia/Hb E patients) was used to treat HepG2 cells, and the effects on hepcidin expression were assayed by real-time quantitative PCR and confocal microscopy.</p> <p><b>Results:</b> Early activation followed by later suppression of hepcidin expression was seen posttreatment. Markedly, however, no significant differences were observed between suppression of hepcidin as mediated by media from the culture of erythroblasts from normal controls and beta0-thalassemia/Hb E patients</p> <p><b>Discussion:</b> Previous studies investigating the suppression of hepcidin expression in beta0-thalassemia/Hb E disease have used patient-derived serum samples, which are complex fluids with contributions from multiple cell types. This study has developed a simple <i>in vitro</i> system that allows investigation of how a single cell type mediates hepcidin expression. The results support proposals that over-suppression of hepcidin seen in beta-thalassemia/Hb E patients is a consequence of the increased mass of erythropoiesis and not defects in the signaling process per se.</p> <p><b>Conclusion:</b> The <i>in vitro</i> cell system developed here allows further investigation into the processes mediating erythroid cell suppression of liver hepcidin expression in both normal and pathological states.</p>