Upregulation of interleukin 6 and granulocyte colony-stimulating factor receptors by transcription factor CCAAT enhancer binding protein α (C/EBPα) is critical for granulopoiesis

Pu Zhang, Atsushi Iwama, Milton W. Datta, Gretchen J. Darlington, Daniel C. Link, Daniel G. Tenen

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Cytokines stimulate granulopoiesis through signaling via receptors whose expression is controlled by lineage-specific transcription factors. Previously, we demonstrated that granulocyte colony-stimulating factor (G- CSF) receptor mRNA was undetectable and granulocyte maturation blocked in CCAAT enhancer binding protein α (C/EBPα)-deficient mice. This phenotype is distinct from that of G-CSF receptor(-/-) mice, suggesting that other genes are likely to be adversely affected by loss of C/EBPα. Here we demonstrate loss of interleukin 6 (IL-6) receptor and IL-6-responsive colony-forming units (CFU-IL6) in C/EBPα(-/-) mice. The observed failure of granulopoiesis could be rescued by the addition of soluble IL-6 receptor and IL-6 or by retroviral transduction of G-CSF receptors, demonstrating that loss of both of these receptors contributes to the absolute block in granulocyte maturation observed in C/EBPα-deficient hematopoietic cells. The results of these and other studies suggest that additional C/EBPα target genes, possibly other cytokine receptors, are also important for the block in granulocyte differentiation observed in vivo in C/EBPα-deficient mice.

Original languageEnglish
Pages (from-to)1173-1184
Number of pages12
JournalJournal of Experimental Medicine
Volume188
Issue number6
DOIs
StatePublished - Sep 21 1998

Keywords

  • CCAAT enhancer binding protein
  • Colony-forming unit
  • Hematopoiesis
  • Knockout mice
  • Myelopoiesis

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