TY - JOUR
T1 - Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene
AU - Unterberger, Claudia
AU - Staples, Karl J.
AU - Smallie, Timothy
AU - Williams, Lynn
AU - Foxwell, Brian
AU - Schaefer, Annette
AU - Kempkes, Bettina
AU - Hofer, T. P.J.
AU - Koeppel, Max
AU - Lohrum, Marion
AU - Stunnenberg, Henk
AU - Frankenberger, Marion
AU - Ziegler-Heitbrock, Loems
N1 - Funding Information:
This work was supported by grants from Deutsche Forschungsgemeinschaft (FR 1454/2-1), Germany, KWF KUN 2003-2926 (The Netherlands, and BBSRC (91-C19230), UK.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - B cells
KW - Cytokines
KW - Human
KW - Inflammation
KW - Transcription factors
UR - https://www.scopus.com/pages/publications/43449100316
U2 - 10.1016/j.molimm.2008.02.020
DO - 10.1016/j.molimm.2008.02.020
M3 - Article
C2 - 18403020
AN - SCOPUS:43449100316
SN - 0161-5890
VL - 45
SP - 3230
EP - 3237
JO - Molecular Immunology
JF - Molecular Immunology
IS - 11
ER -