Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression.
IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive. IL-10 is regulated at the level of transcription, but the critical motifs and the relevant transcription factors controlling this gene have remained elusive to date. We now report that a sequence at -120 bp in the human IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced trans-activation. Overexpression of dominant negative Stat3 suppresses promoter activity, while wild-type Stat3 leads to an enhancement of this activity. Our results show that Stat3, by binding to a single motif in the IL-10 promoter, is controlling expression of the human IL-10 gene.
Benkhart
E M
EM
Institute for Immunology, University of Munich, Munich, Germany; Institute of Mammalian Genetics, Neuherberg, Germany; and Genomatix Software GmbH, Munich, Germany.
Siedlar
M
M
Wedel
A
A
Werner
T
T
Ziegler-Heitbrock
H W
HW
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D005822:Genetic Vectors / Q000138:chemical synthesis; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000276:immunology; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology; D014162:Transfection / Q000276:immunology
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016753:Interleukin-10