title: Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene.
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.
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Unterberger
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Staples
authors.forename: Timothy
authors.initials: T
authors.lastname: Smallie
authors.forename: Lynn
authors.initials: L
authors.lastname: Williams
authors.forename: Brian
authors.initials: B
authors.lastname: Foxwell
authors.forename: Annette
authors.initials: A
authors.lastname: Schaefer
authors.forename: Bettina
authors.initials: B
authors.lastname: Kempkes
authors.forename: T P J
authors.initials: TP
authors.lastname: Hofer
authors.forename: Max
authors.initials: M
authors.lastname: Koeppel
authors.forename: Marion
authors.initials: M
authors.lastname: Lohrum
authors.forename: Henk
authors.initials: H
authors.lastname: Stunnenberg
authors.forename: Marion
authors.initials: M
authors.lastname: Frankenberger
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D016753:Interleukin-10; D008156:Luciferases; D008775:Methylprednisolone