Granulocyte colony-stimulating factor induces the binding of STAT1 and STAT3 to the IFNgamma response region within the promoter of the Fc(gamma)RI/CD64 gene in human neutrophils.
Granulocyte colony-stimulating factor (G-CSF) has been recently shown to induce the high-affinity Fc receptor for IgG (Fc(gammaRI)/CD64) in human polymorphonuclear neutrophils (PMN). To elucidate the molecular mechanisms whereby G-CSF exerts this effect, we examined whether the cytokine induces the binding of transcription factors to the IFNgamma response region (GRR), a well characterized regulatory element in the Fc(gammaRI) promoter that is responsible for the transcriptional induction of this gene. Using electrophoretic mobility shift assays, we show that in human PMN, G-CSF activates a GRR-binding complex which contains members of the signal transducer and activator of transcription (STAT) family of proteins, namely STAT1 and STAT3. In keeping with this result, treatment of neutrophils with G-CSF led to tyrosine phosphorylation of STAT3, as determined by immunoprecipitation followed by immunoblotting with antiphosphotyrosine antibodies. This is the first demonstration that in human neutrophils, the induction by G-CSF of Fc(gammaRI) gene expression may be mediated by the binding of STAT1 and STAT3 to the GRR sequence.
Bovolenta
C
C
Department of General Pathology, University of Verona, Italy.
Gasperini
S
S
Cassatella
M A
MA
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma; D009504:Neutrophils / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma