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Published on: April 14, 2010
Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression
E M Benkhart1, M Siedlar, A Wedel
1Institute for Immunology, University of Munich, Munich, Germany; Institute of Mammalian Genetics, Neuherberg, Germany; and Genomatix Software GmbH, Munich, Germany.
Abstract:
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.
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