Abstract
Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.
Keywords:
bone marrow; dendritic cells; inflammation; iron overload.
MeSH terms
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Animals
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Arginase / genetics
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Arginase / metabolism
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Bone Marrow / drug effects
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Bone Marrow / metabolism*
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Bone Marrow Cells / metabolism
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CD11c Antigen / metabolism*
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Cell Differentiation / physiology*
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Cytokines / metabolism
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism*
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Gene Expression Regulation
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Hematopoiesis
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Histocompatibility Antigens Class II / metabolism*
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Inflammation
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / metabolism
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Iron Overload / metabolism*
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Lipopolysaccharides / adverse effects
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Mice
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / metabolism
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Trans-Activators / metabolism
Substances
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CD11c Antigen
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Cytokines
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Histocompatibility Antigens Class II
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Interferon Regulatory Factors
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Lipopolysaccharides
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Proto-Oncogene Proteins
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Trans-Activators
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interferon regulatory factor-8
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proto-oncogene protein Spi-1
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Arg1 protein, mouse
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Arginase