Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene
| Autor: | Bettina Kempkes, Claudia Unterberger, Max Koeppel, Brian M. J. Foxwell, Loems Ziegler-Heitbrock, Marion Frankenberger, Thomas Höfer, Marion Lohrum, Henk Stunnenberg, Timothy Smallie, Karl J. Staples, Lynn M. Williams, Annette Schaefer |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
STAT3 Transcription Factor
Chromatin Immunoprecipitation Immunology Biology Methylprednisolone CD19 Adenoviridae Cell Line Genes Reporter medicine Humans RNA Messenger Luciferases Promoter Regions Genetic STAT3 Molecular Biology Transcription factor Gene Genes Dominant Sequence Deletion Regulation of gene expression Messenger RNA Molecular biology Interleukin-10 Gene Expression Regulation Cell culture biology.protein Glucocorticoid Protein Binding medicine.drug |
| Zdroj: | Molecular Immunology, 45, 3230-3237 Molecular Immunology, 45, 11, pp. 3230-3237 |
| ISSN: | 0161-5890 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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