The Journal of Immunology · 2000 · 252 citations · 23 references
Life SciencesImmunologyMolecular BiologyGene ExpressionInflammationTranscriptional RegulationCytokine BiologyCytokine RegulationCytokine SignalingImmune Gene RegulationInflammatory SignalingInnate Immune Signaling PathwaysCytokine Expression RegulationInterleukin RegulationInterleukin-10 Mediated ImmunosuppressionPromoter Activity AnalysisStat3 Signaling
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.
23