Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation
In: International Journal of Hematology, Jg. 95 (2012-05-03), S. 640-647
Online
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Zugriff:
The zinc finger transcriptional repressor Gfi-1 has been shown to play a critical role in early granulopoiesis; however, its role in late neutrophilic development is poorly understood. We report here that forced expression of a dominant negative Gfi-1 mutant, N382S, resulted in augmented mRNA levels of eosinophil major basic protein (MBP) in myeloid cells induced with G-CSF to undergo terminal neutrophilic differentiation. MBP is a cytotoxic protein that is abundantly expressed in eosinophils, but not in neutrophils. Ectopic expression of MBP inhibited the proliferation and survival of differentiating myeloid cells in response to G-CSF. Significantly, while GFI-1 is upregulated during neutrophilic differentiation, it is rapidly downregulated upon induction of eosinophilic differentiation, which was associated with increased MBP expression. Knockdown of GFI-1 in eosinophilic cells also led to increased level of MBP mRNA. These results indicate that Gfi-1 functions to inhibit the expression of MBP and aberrant expression of MBP as a result of loss of Gfi-1 function may cause premature apoptosis of differentiating neutrophils. In contrast, the rapid downregulation of Gfi-1 during eosinophilic development may allow for abundant expression of MBP, a hallmark of eosinophilic differentiation.
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Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation
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Autor/in / Beteiligte Person: | Dong, Fan ; Liu, Qingquan |
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Zeitschrift: | International Journal of Hematology, Jg. 95 (2012-05-03), S. 640-647 |
Veröffentlichung: | Springer Science and Business Media LLC, 2012 |
Medientyp: | unknown |
ISSN: | 1865-3774 (print) ; 0925-5710 (print) |
DOI: | 10.1007/s12185-012-1078-x |
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