Abstract
IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on proinflammatory mediator production. In this study we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3, and a helicase family corepressor, Strawberry notch homologue 2 (SBNO2), in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3 and a stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway regulated by IL-10 but not by STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 repressed NF-kappaB- but not IFN regulatory factor 7 (IRF7)-activated transcriptional reporters. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cell Line
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology*
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Humans
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Interleukin-10 / genetics
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Interleukin-10 / pharmacology
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Interleukin-10 / physiology*
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Macrophages / drug effects
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Macrophages / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Proto-Oncogene Proteins c-ets / drug effects
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Proto-Oncogene Proteins c-ets / genetics
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Proto-Oncogene Proteins c-ets / physiology*
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Small Interfering / pharmacology
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Repressor Proteins / drug effects
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / physiology*
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Signal Transduction / drug effects
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Signal Transduction / immunology*
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Time Factors
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Transcription Factors / drug effects
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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ETV3 protein, human
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ETV3 protein, mouse
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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RNA, Small Interfering
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Repressor Proteins
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SBNO2 protein, human
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SBNO2 protein, mouse
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Transcription Factors
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Interleukin-10