Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene.
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.
Unterberger
Claudia
C
Clinical Cooperation Group, Inflammatory Lung Diseases, Helmholtz Zentrum München, German Research Center for Environmental Health and Asklepios-Fachklinik, Robert-Koch-Allee 29, 82131 Gauting, Germany.
Staples
Karl J
KJ
Smallie
Timothy
T
Williams
Lynn
L
Foxwell
Brian
B
Schaefer
Annette
A
Kempkes
Bettina
B
Hofer
T P J
TP
Koeppel
Max
M
Lohrum
Marion
M
Stunnenberg
Henk
H
Frankenberger
Marion
M
Ziegler-Heitbrock
Loems
L
D000256:Adenoviridae; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D017384:Sequence Deletion
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D016753:Interleukin-10; D008156:Luciferases; D008775:Methylprednisolone