title: Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D047093:Eosinophil Major Basic Protein / Q000235:genetics* / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D047093:Eosinophil Major Basic Protein