Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.molimm.2008.02.020

Type

Journal article

Journal

Mol immunol

Publication Date

06/2008

Volume

45

Pages

3230 - 3237

Keywords

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