Role of Stat3 in Lipopolysaccharide-Induced IL-10 Gene Expression
Author(s) -
Elke Benkhart,
Maciej Siedlar,
Angela Wedel,
Thomas Werner,
HW Ziegler-Heitbrock
Publication year - 2000
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.165.3.1612
Subject(s) - stat3 , gene , transcription (linguistics) , promoter , promoter activity , microbiology and biotechnology , stat , transcription factor , gene expression , biology , sequence motif , cytokine , genetics , linguistics , philosophy
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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