title: IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3.
abstract: IL-10 is an important immunosuppressive cytokine that can down-regulate expression of other cytokines and has been shown to down-regulate itself. We show, in this study, that treatment of human monocyte-derived macrophages with IL-10 induces IL-10 mRNA in a dose- and time-dependent manner with an optimum induction at 100 ng/ml and at 6 h, whereas IL-10-induced IL-10 protein can be detected at 18 h. In the same cells, IL-10 can partially suppress IL-10 mRNA induced by LPS, but only down to the level of IL-10-induced IL-10. An adenoviral luciferase reporter construct driven by the -195 IL-10 promoter, which contains a Stat motif, was readily induced by both IL-10 and LPS. Mutation of this Stat motif ablated IL-10 activation of this promoter, but not the LPS activation. Finally, we show that overexpression of a dominant-negative Stat3 protein will prevent IL-10 induction, but not LPS induction, of IL-10 mRNA. These data show that IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Staples
authors.forename: Timothy
authors.initials: T
authors.lastname: Smallie
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Williams
authors.forename: Andy
authors.initials: A
authors.lastname: Foey
authors.forename: Bernie
authors.initials: B
authors.lastname: Burke
authors.forename: Brian M J
authors.initials: BM
authors.lastname: Foxwell
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10