Numerous transcription factors allow haematopoietic cells to respond to lineage- and stage-specific cytokines and to act as their effectors. It is increasingly evident that the interferon regulatory factor-1 (IRF-1) transcription factor can selectively regulate different sets of genes depending on the cell type and/or the nature of cellular stimuli, evoking distinct responses in each. In the present study, we investigated mechanisms underlying the differentiation-inducing properties of granulocytic colony-stimulating factor (G-CSF) and whether IRF transcription factors are functionally relevant in myeloid differentiation. Both normal human progenitors and murine 32Dcl3 myeloblasts induced to differentiate along the granulocytic pathway showed an up-regulation of IRF-1 expression. Ectopic expression of IRF-1 did not abrogate the growth factor requirement of 32Dcl3 cells, although a small percentage of cells that survived cytokine deprivation differentiated fully to neutrophils. Moreover, in the presence of G-CSF, granulocytic differentiation of IRF-1-expressing cells was accelerated, as assessed by morphology and expression of specific differentiation markers. Down-modulation of c-Myb protein and direct stimulation of lysozyme promoter activity by IRF-1 were also observed. Conversely, constitutive expression of IRF-2, a repressor of IRF-1 transcriptional activity, completely abrogated the G-CSF-induced neutrophilic maturation. We conclude that IRF-1 exerts a pivotal role in granulocytic differentiation and that its induction by G-CSF represents a limiting step in the early events of differentiation.
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December 2001
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Research Article|
November 26 2001
Ectopic expression of interferon regulatory factor-1 potentiates granulocytic differentiation
Eliana M. COCCIA;
Eliana M. COCCIA
∗Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
†Laboratory of Immunology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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Emilia STELLACCI;
Emilia STELLACCI
∗Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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Mauro VALTIERI;
Mauro VALTIERI
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
§Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107-5541, U.S.A.
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Barbara MASELLA;
Barbara MASELLA
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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Tiziana FECCIA;
Tiziana FECCIA
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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Giovanna MARZIALI;
Giovanna MARZIALI
∗Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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John HISCOTT;
John HISCOTT
∥Molecular Oncology Group, Lady Davis Institute, McGill University, Montreal, Quebec, Canada, H3T 1E2
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Ugo TESTA;
Ugo TESTA
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
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Cesare PESCHLE;
Cesare PESCHLE
‡Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
§Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107-5541, U.S.A.
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Angela BATTISTINI
Angela BATTISTINI
1
∗Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy
1To whom correspondence should be addressed (e-mail battist@iss.it).
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Publisher: Portland Press Ltd
Received:
June 15 2001
Revision Received:
August 13 2001
Accepted:
September 25 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 360 (2): 285–294.
Article history
Received:
June 15 2001
Revision Received:
August 13 2001
Accepted:
September 25 2001
Citation
Eliana M. COCCIA, Emilia STELLACCI, Mauro VALTIERI, Barbara MASELLA, Tiziana FECCIA, Giovanna MARZIALI, John HISCOTT, Ugo TESTA, Cesare PESCHLE, Angela BATTISTINI; Ectopic expression of interferon regulatory factor-1 potentiates granulocytic differentiation. Biochem J 1 December 2001; 360 (2): 285–294. doi: https://doi.org/10.1042/bj3600285
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