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), 3230-3237. (doi:10.1016/j.molimm.2008.02.020). (PMID:18403020).

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Description/Abstract

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
ISSNs: 0161-5890 (print)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
R Medicine > RB Pathology
Divisions: University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
Item ID: 185833
Date Deposited: 11 May 2011 10:16
Last Modified: 26 Apr 2013 00:20
Contributors: Unterberger, Claudia (Author)
Staples, Karl J. (Author)
Smallie, Timothy (Author)
Williams, Lynn (Author)
Foxwell, Brian (Author)
Schaefer, Annette (Author)
Kempkes, Bettina (Author)
Hofer, T.P.J. (Author)
Koeppel, Max (Author)
Lohrum, Marion (Author)
Stunnenberg, Henk (Author)
Frankenberger, Marion (Author)
Ziegler-Heitbrock, Loems (Author)
Date: June 2008
Status: Published
URI: http://eprints.soton.ac.uk/id/eprint/185833

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