Impaired myelopoiesis in mice devoid of interferon regulatory factor 1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-11

AUTHORS

U Testa, E Stellacci, E Pelosi, P Sestili, M Venditti, R Orsatti, A Fragale, E Petrucci, L Pasquini, F Belardelli, L Gabriele, A Battistini

ABSTRACT

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. More... »

PAGES

1864-1871

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2403472

DOI

http://dx.doi.org/10.1038/sj.leu.2403472

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041559616

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15385939


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