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.
Journal article
2008-06-01T00:00:00+00:00
45
3230 - 3237
7
Adenoviridae, Cell Line, Chromatin Immunoprecipitation, Gene Expression Regulation, Genes, Dominant, Genes, Reporter, Humans, Interleukin-10, Luciferases, Methylprednisolone, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, STAT3 Transcription Factor, Sequence Deletion