Interleukin-6 directly impairs the erythroid development of human TF-1 erythroleukemic cells

Bryan J. McCranor, Min Jung Kim, Nicole M. Cruz, Qian Li Xue, Alan E. Berger, Jeremy D. Walston, Curt I. Civin, Cindy Roy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalBlood Cells, Molecules, and Diseases
Volume52
Issue number2-3
DOIs
StatePublished - Feb 1 2014

Keywords

  • Anemia
  • Cytokine
  • Erythropoiesis
  • Hemoglobin
  • Inflammation
  • Mitochondria

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

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