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), increases incorporation of [3H]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 was used to identify and clone GM‐CSF‐responsive mRNAs. Serum‐ and glucocorticoid‐regulated kinase (sgk) mRNA was identified that could be up‐regulated 10‐ to 20‐fold by ≥0.1 ng/mL recombinant human GM‐CSF. The 2.6‐kb sgk mRNA was induced rapidly (within 30 min) by GM‐CSF and remained at high levels for at least 12 h. Up‐regulation was blocked completely 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. Other inflammatory mediators could also increase sgk mRNA levels (GM‐CSF > > lipopolysaccharide > fMLP = tumor necrosis factor α). The function of sgk in granulocytes remains unknown. J. Leukoc. Biol. 67: 240–248; 2000.