Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression

IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppre ssive. IL-10 is regulated at the level of transcription, but the critical m oths and the relevant transcription factors controlling this gene have rema ined elusive to date. We now report that a sequence at - 120 bp in the huma n IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this m otif abrogates LPS-induced trans-activation. Overexpression of dominant neg ative Stat3 suppresses promoter activity, while wild-type Stall 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.