IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor stat3

Karl J. Staples, Timothy Smallie, Lynn M. Williams, Andy Foey, Bernie Burke, Brian M.J. Foxwell, Loems Ziegler-Heitbrock

Research output: Contribution to journalArticle

101 Citations (Scopus)

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-107. 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.

Original languageEnglish
Pages (from-to)4779-4785
Number of pages7
JournalJournal of Immunology
Volume178
Issue number8
DOIs
Publication statusPublished - 15 Apr 2007
Externally publishedYes

Keywords

  • Adenoviridae/genetics
  • Humans
  • Interleukin-10/genetics
  • Lipopolysaccharides/pharmacology
  • Macrophages/immunology
  • Monocytes/cytology
  • Promoter Regions, Genetic
  • RNA, Messenger/analysis
  • STAT3 Transcription Factor/physiology

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Staples, K. J., Smallie, T., Williams, L. M., Foey, A., Burke, B., Foxwell, B. M. J., & Ziegler-Heitbrock, L. (2007). IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor stat3. Journal of Immunology, 178(8), 4779-4785. https://doi.org/10.4049/jimmunol.178.8.4779