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

P Zhang, A Iwama, MW Datta, GJ Darlington… - The Journal of …, 1998 - rupress.org
P Zhang, A Iwama, MW Datta, GJ Darlington, DC Link, DG Tenen
The Journal of experimental medicine, 1998rupress.org
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 …
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.
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