Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 428K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, P. Articles by Tenen, D. G. Search for Related Content PubMed PubMed Citation Articles by Zhang, P. Articles by Tenen, D. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Social Bookmarking                            What's this?

Articles

Upregulation of Interleukin 6 and Granulocyte Colony-Stimulating Factor Receptors by Transcription Factor CCAAT Enhancer Binding Protein (C/EBP) Is Critical for Granulopoiesis

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

From the ^* Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215; the Department of Pathology and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030; and the Division of Bone Marrow Transplantation and Stem Cell Biology, Department of Medicine, Washington University Medical School, St. Louis, Missouri 63110-1093

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 (C/EBP)-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/EBP. Here we demonstrate loss of interleukin 6 (IL-6) receptor and IL-6–responsive colony-forming units (CFU-IL6) in C/EBP^–/– 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/EBP-deficient hematopoietic cells. The results of these and other studies suggest that additional C/EBP target genes, possibly other cytokine receptors, are also important for the block in granulocyte differentiation observed in vivo in C/EBP-deficient mice.

Key Words: CCAAT enhancer binding protein • knockout mice • colony-forming unit • hematopoiesis • myelopoiesis

Abbreviations used: C/EBP, CCAAT enhancer binding protein; CFU-GM, GM-CSF–responsive CFU; CFU-IL3 and -IL6, IL-3 and IL-6–responsive CFU, respectively; RT, reverse transcription; SCF, stem cell factor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS