Expression of serum- and glucocorticoid-regulated kinase (sgk) mRNA is up-regulated by GM-CSF and other proinflammatory mediators in human granulocytes

Stimulation of human peripheral blood granulocytes with the proinflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), incre ases incorporation of [H-3]uridine into RNA. We investigated the nature of the RNA synthesized under these conditions, Using transcription inhibitors, gel electrophoresis, and high-salt precipitation, it was concluded that as much as 90% of this radiolabeled RNA represents polymerase II transcripts, Differential display reverse transcription-polymerase chain reaction tvas used to identify and clone GM-CSF-responsive mRNAs. Serum- and glucocortico id-regulated kinase (sgk) mRNA was identified that could be up-regulated 10 - to 20-fold by greater than or equal to 0.1 ng/mL recombinant human GM-CSF . The 2.6-kb sgk mRNA was induced rapidly (within 30 min) by GM-CSF and rem ained at high levels for at least 12 h, Up-regulation was blocked completel y by the transcription inhibitor, actinomycin D, but not by the translation inhibitor, cycloheximide, nor by the tyrosine kinase inhibitor, genistein, Up-regulation did not appear to be caused by enhanced mRNA stability, Othe r inflammatory mediators could also increase sgk mRNA levels (GM-CSF >> lip opolysaccharide > fMLP = tumor necrosis factor alpha), The function of sgk in granulocytes remains unknown.