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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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.
|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
|Date Deposited:||11 May 2011 10:16|
|Last Modified:||27 Mar 2014 19:40|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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