Granulocyte colony-stimulating factor induces the binding of STAT1 and STAT3 to the IFN gamma 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 gamma RI/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 IFN gamma response region (GRR), a well characterized regulatory element in the Fc gamma RI 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 gamma RI gene expression may be mediated by the binding of STAT1 and STAT3 to the GRR sequence.