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Interleukin-6 directly impairs the erythroid development of human TF-1 erythroleukemic cells.
- Source :
-
Blood cells, molecules & diseases [Blood Cells Mol Dis] 2014 Feb-Mar; Vol. 52 (2-3), pp. 126-33. Date of Electronic Publication: 2013 Oct 09. - Publication Year :
- 2014
-
Abstract
- Anemia of inflammation or chronic disease is a highly prevalent form of anemia. The inflammatory cytokine interleukin-6 (IL-6) negatively correlates with hemoglobin concentration in many disease states. The IL-6-hepcidin antimicrobial peptide axis promotes iron-restricted anemia; however the full role of IL-6 in anemia of inflammation is not well-defined. We previously reported that chronic inflammation had a negative impact on maturation of erythroid progenitors in a mouse model. We hypothesized that IL-6 may be responsible for impaired erythropoiesis, independent of iron restriction. To test the hypothesis we utilized the human erythroleukemia TF-1 cell line to model erythroid maturation and exposed them to varying doses of IL-6 over six days. At 10 ng/ml, IL-6 significantly repressed erythropoietin-dependent TF-1 erythroid maturation. While IL-6 did not decrease the expression of genes associated with hemoglobin synthesis, we observed impaired hemoglobin synthesis as demonstrated by decreased benzidine staining. We also observed that IL-6 down regulated expression of the gene SLC4a1 which is expressed late in erythropoiesis. Those findings suggested that IL-6-dependent inhibition of hemoglobin synthesis might occur. We investigated the impact of IL-6 on mitochondria. IL-6 decreased the mitochondrial membrane potential at all treatment doses, and significantly decreased mitochondrial mass at the highest dose. Our studies indicate that IL-6 may impair mitochondrial function in maturing erythroid cells resulting in impaired hemoglobin production and erythroid maturation. Our findings may indicate a novel pathway of action for IL-6 in the anemia of inflammation, and draw attention to the potential for new therapeutic targets that affect late erythroid development.<br /> (© 2013.)
- Subjects :
- Antigens, Surface metabolism
Cell Line, Tumor
Erythropoiesis genetics
Humans
Immunophenotyping
Leukemia, Erythroblastic, Acute metabolism
Leukemia, Erythroblastic, Acute pathology
Membrane Potential, Mitochondrial drug effects
Mitochondria drug effects
Mitochondria metabolism
Reactive Oxygen Species metabolism
Erythropoiesis drug effects
Interleukin-6 pharmacology
Leukemia, Erythroblastic, Acute etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0961
- Volume :
- 52
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Blood cells, molecules & diseases
- Publication Type :
- Academic Journal
- Accession number :
- 24119518
- Full Text :
- https://doi.org/10.1016/j.bcmd.2013.09.004