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

In these studies, we examined signaling through the transcription factor STAT5 in human peripheral blood eosinophils after treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-5. In response to either cytokine, STAT5 was rapidly tyrosine phosphorylated and acquired interferon gamma activation site (GAS) DNA binding activity. Tyrosine-phosphorylated STAT5 was associated with both cytosolic and nuclear cell fractions. Consistent with activation, the transcription of a STAT5-dependent gene, cytokine inducible, SH2-containing protein (CIS1), was enhanced after cytokine stimulation. This is the first report of IL-5 regulation of CIS1 gene expression in any cell type. Given its role in cytokine signaling, CIS1 upregulation may serve to attenuate IL-5 and GM-CSF modulation of eosinophil function. These data suggest that active nuclear STAT5 participates in the regulation of IL-5 and GM-CSF--inducible genes in stimulated human peripheral blood eosinophils.