Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene

Unterberger, Claudia, Staples, Karl J., Smallie, Timothy, Williams, Lynn, Foxwell, Brian, Schaefer, Annette, Kempkes, Bettina, Hofer, T.P.J., Koeppel, Max, Lohrum, Marion, Stunnenberg, Henk, Frankenberger, Marion and Ziegler-Heitbrock, Loems (2008) Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene Molecular Immunology, 45, (11), pp. 3230-3237. (doi:10.1016/j.molimm.2008.02.020). (PMID:18403020).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.molimm.2008.02.020
ISSNs: 0161-5890 (print)

ePrint ID: 185833
Date :
Date Event
June 2008Published
Date Deposited: 11 May 2011 10:16
Last Modified: 18 Apr 2017 02:15
Further Information:Google Scholar

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