期刊
MOLECULAR IMMUNOLOGY
卷 45, 期 11, 页码 3230-3237出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2008.02.020
关键词
human; B cells; cytokines; inflammation; transcription factors
资金
- Biotechnology and Biological Sciences Research Council [91-C19230] Funding Source: Medline
- Medical Research Council [G0700128] Funding Source: Medline
- MRC [G0700128] Funding Source: UKRI
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-immumoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3. (C) 2008 Elsevier Ltd. All rights reserved.
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