Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene.

Claudia Unterberger, Karl J Staples, Timothy Smallie, Lynn Williams, Brian Foxwell, Annette Schaefer, Bettina Kempkes, T P J Hofer, Max Koeppel, Marion Lohrum, Henk Stunnenberg, Marion Frankenberger, Loems Ziegler-Heitbrock

Index: Mol. Immunol. 45 , 3230-7, (2008)

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Abstract

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 of 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 trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative 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-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.