Impaired myelopoiesis in mice devoid of interferon regulatory factor 1.
Interferon regulatory factor (IRF)-1 is a transcription factor controlling the expression of several genes, which are differentially induced depending on the cell type and signal. IRF-1 modulates multiple functions, including regulation of immune responses and host defence, cell growth, cytokine signalling and hematopoietic development. Here, we investigated the role of IRF-1 in granulocytic differentiation in mice with a null mutation in the IRF-1 gene. We show that IRF-1(-/-) bone marrow cells exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements as compared to normal mice, suggestive of a defective maturation process. Clonogenetic analyses revealed a reduced number of CFU-G, CFU-M and CFU-GM colonies in IRF-1(-/-) mice, while the number of BFU-E/CFU-E colonies was unchanged. At the molecular level, the expression of CAAT-enhancer-binding protein (C/EBP)-epsilon, -alpha and PU.1 was substantially lower in the CD11b(+) cells from the bone marrow of IRF-1(-/-) mice as compared to cells from wild-type mice. These results, together with the fact that IRF-1 is markedly induced early during granulo-monocytic differentiation of CD34+ cells, highlight the pivotal role of IRF-1 in the early phases of myelopoiesis.
Testa
U
U
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Stellacci
E
E
Pelosi
E
E
Sestili
P
P
Venditti
M
M
Orsatti
R
R
Fragale
A
A
Petrucci
E
E
Pasquini
L
L
Belardelli
F
F
Gabriele
L
L
Battistini
A
A
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015672:Erythroid Precursor Cells; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006720:Homozygote; D050856:Interferon Regulatory Factor-1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D038042:Myelopoiesis / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; D039481:CD11b Antigen; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C489468:Cebpe protein, mouse; C494258:Irf1 protein, mouse