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Unterberger, C.* ; Staples, K.J.* ; Smallie, T.* ; Williams, L.* ; Foxwell, B.* ; Schaefer, A.* ; Kempkes, B. ; Hofer, T.P.* ; Koeppel, M.* ; Lohrum, M.* ; Stunnenberg, H.* ; Frankenberger, M.* ; Ziegler-Heitbrock, L.

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

Mol. Immunol. 45, 3230-3237 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Human; B cells; Cytokines; Inflammation; Transcription factors
ISSN (print) / ISBN 0161-5890
e-ISSN 1872-9142
Quellenangaben Volume: 45, Issue: 11, Pages: 3230-3237 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Inflammatory Lung Diseases (CPC-KEL)
Research Unit Gene Vector (AGV)