Role of Stat3 in Glucocorticoid-induced Expression of the human IL-10 Gene
journal contributionposted on 23.06.2008, 15:33 by Claudia Unterberger, Karl J. Staples, Timothy Smallie, Lynn M. Williams, Brian Foxwell, Annette Schaefer, Bettina Kempkes, T. P. J. Hofer, Max Koeppel, Marion Lohrum, Henk Stunnenberg, Marion Frankenberger, Loems Ziegler-Heitbrock
In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment cells with MP at 10-6 M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the - 120 STAT-motif strongly reduced MP induced transactivation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominantnegative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immuno-precipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.