Granulocyte macrophage colony-stimulating factor and interleukin-5 activate STAT5 and induce CIS1 mRNA in human peripheral blood eosinophils

In these studies, we examined signaling through the transcription factor ST AT5 in human peripheral blood eosinophils after treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-5, In res ponse to either cytokine, STAT5 was rapidly tyrosine phosphorylated and acq uired interferon gamma activation site (GAS) DNA binding activity. Tyrosine -phosphorylated STAT5 was associated with both cytosolic and nuclear cell f ractions. Consistent with activation, the transcription of a STAT5-dependen t gene, cytokine inducible, SH2-containing protein (CIS1), was enhanced aft er cytokine stimulation. This is the first report of IL-S regulation of CIS 1 gene expression in any cell type. Given its role in cytokine signaling, C IS1 upregulation may serve to attenuate IL-5 and GM-CSF modulation of eosin ophil function. These data suggest that active nuclear STAT5 participates i n the regulation of IL-5 and GM-CSF-inducible genes in stimulated human per ipheral blood eosinophils.