MIMM-D-07-00686 revised Unterberger GC IL-10MIF.pdf (406.1 kB)
Role of Stat3 in Glucocorticoid-induced Expression of the human IL-10 Gene
journal contribution
posted on 2008-06-23, 15:33 authored 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-HeitbrockIn 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.
