scholarly journals Granulocyte Colony Stimulating Factor Induces Lipopolysaccharide (LPS) Sensitization via Upregulation of LPS Binding Protein in Rat

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56654 ◽  
Author(s):  
Haoshu Fang ◽  
Anding Liu ◽  
Jian Sun ◽  
Alexandra Kitz ◽  
Olaf Dirsch ◽  
...  
Keyword(s):  
Binding Protein ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Lps Binding

Granulocyte colony-stimulating factor regulates myeloid differentiation through CCAAT/enhancer-binding protein ε

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 897-905 ◽  
Author(s):  
Hideaki Nakajima ◽  
James N. Ihle
Keyword(s):  
Molecular Mechanisms ◽  
Binding Protein ◽  
Hematopoietic Cells ◽  
Myeloid Differentiation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Granulocytic Differentiation ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Stimulating Factor

Granulocyte colony-stimulating factor (G-CSF) is a major cytokine that regulates proliferation and differentiation of myeloid cells, although the underlying mechanisms by which G-CSF controls myeloid differentiation are largely unknown. Differentiation of hematopoietic cells is regulated by lineage-specific transcription factors, and gene-targeting studies previously revealed the critical roles of CCAAT/enhancer-binding protein (C/EBP) α and C/EBPε, respectively, in the early and mid-late stages of granulocyte differentiation. The expression of C/EBPε in 32Dcl3 cells and FDCP1 cells expressing mutant G-CSF receptors was examined and it was found that G-CSF up-regulates C/EBPε. The signal for this expression required the region containing the first tyrosine residue of G-CSF receptor. Dominant-negative signal transducers and activators of transcription 3 blocked G-CSF–induced granulocytic differentiation in 32D cells but did not block induction of C/EBPε, indicating that these proteins work in different pathways. It was also found that overexpression of C/EBPε greatly facilitated granulocytic differentiation by G-CSF and, surprisingly, that expression of C/EBPε alone was sufficient to make cells differentiate into morphologically and functionally mature granulocytes. Overexpression of c-myc inhibits differentiation of hematopoietic cells, but the molecular mechanisms of this inhibition are not fully understood. In 32Dcl3 cells overexpressing c-myc that do not differentiate by means of G-CSF, induction of C/EBPε is completely abrogated. Ectopic expression of C/EBPε in these cells induced features of differentiation, including changes in nuclear morphologic characteristics and the appearance of granules. These data show that C/EBPε constitutes a rate-limiting step in G-CSF–regulated granulocyte differentiation and that c-myc antagonizes G-CSF–induced myeloid differentiation, at least partly by suppressing induction of C/EBPε.

AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the up-regulation of CCAAT/enhancer binding protein epsilon

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 288-296 ◽  
Author(s):  
Kimiko Shimizu ◽  
Issay Kitabayashi ◽  
Nanao Kamada ◽  
Tatsuo Abe ◽  
Nobuo Maseki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Precursor Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
G Cells ◽  
Enhancer Binding Protein ◽  
Dependent Cell ◽  
Stimulating Factor

The t(8;21) translocation is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). In this translocation, the AML1 (CBFA2/PEBP2aB) gene is disrupted and fused to the MTG8 (ETO) gene. The ectopic expression of the resulting AML1-MTG8 fusion gene product in L-G and 32Dcl3 murine myeloid precursor cells stimulates cell proliferation without inducing morphologic terminal differentiation into mature granulocytes in response to granulocyte-colony stimulating factor (G-CSF). This study found that the ectopic expression of AML1-MTG8 elevates the expression of the G-CSF receptor (G-CSFR). Analysis of the promoter region of the G-CSFR gene revealed that up-regulation of G-CSFR expression by AML1-MTG8 does not depend on the AML1-binding sequence, but on the C/EBP (CCAAT/enhancer binding protein) binding site. The results suggest that the overproduction of G-CSFR is at least partly mediated by C/EBPɛ, whose expression is activated by AML1-MTG8. The ectopic expression of G-CSFR in L-G cells induced cell proliferation in response to G-CSF, but did not inhibit cell differentiation into mature neutrophils. Overexpression of C/EBPɛ in L-G cells also stimulated G-CSF–dependent cell proliferation. High expression levels of G-CSFR were also found in the leukemic cells of AML patients with t(8;21). Therefore, G-CSF–dependent cell proliferation of myeloid precursor cells may be implicated in leukemogenesis.

AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the up-regulation of CCAAT/enhancer binding protein epsilon

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 288-296 ◽  
Author(s):  
Kimiko Shimizu ◽  
Issay Kitabayashi ◽  
Nanao Kamada ◽  
Tatsuo Abe ◽  
Nobuo Maseki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Precursor Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
G Cells ◽  
Enhancer Binding Protein ◽  
Dependent Cell ◽  
Stimulating Factor

Abstract The t(8;21) translocation is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). In this translocation, the AML1 (CBFA2/PEBP2aB) gene is disrupted and fused to the MTG8 (ETO) gene. The ectopic expression of the resulting AML1-MTG8 fusion gene product in L-G and 32Dcl3 murine myeloid precursor cells stimulates cell proliferation without inducing morphologic terminal differentiation into mature granulocytes in response to granulocyte-colony stimulating factor (G-CSF). This study found that the ectopic expression of AML1-MTG8 elevates the expression of the G-CSF receptor (G-CSFR). Analysis of the promoter region of the G-CSFR gene revealed that up-regulation of G-CSFR expression by AML1-MTG8 does not depend on the AML1-binding sequence, but on the C/EBP (CCAAT/enhancer binding protein) binding site. The results suggest that the overproduction of G-CSFR is at least partly mediated by C/EBPɛ, whose expression is activated by AML1-MTG8. The ectopic expression of G-CSFR in L-G cells induced cell proliferation in response to G-CSF, but did not inhibit cell differentiation into mature neutrophils. Overexpression of C/EBPɛ in L-G cells also stimulated G-CSF–dependent cell proliferation. High expression levels of G-CSFR were also found in the leukemic cells of AML patients with t(8;21). Therefore, G-CSF–dependent cell proliferation of myeloid precursor cells may be implicated in leukemogenesis.

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

1998 ◽  
Vol 188 (6) ◽  
pp. 1173-1184 ◽  
Author(s):  
Pu Zhang ◽  
Atsushi Iwama ◽  
Milton W. Datta ◽  
Gretchen J. Darlington ◽  
Daniel C. Link ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Target Genes ◽  
Binding Protein ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Stimulating Factor ◽  
Deficient Mice

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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