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SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth |
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Published in | Cancer Research. 2013, vol. 73, no. 12, p. 3578-90 | |
Abstract | Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4 T cells derived from mice fed a DHA-enriched diet displayed less capability to differentiate into TH17 cells. In two different mouse models of cancer, DHA prevented tumor outgrowth and angiogenesis in an IL-17-dependent manner. Altogether, our results uncover a novel molecular pathway by which PPARγ-induced SOCS3 expression prevents IL-17-mediated cancer growth. | |
Keywords | Animals — Blotting, Western — CD4-Positive T-Lymphocytes/drug effects/metabolism — Cell Differentiation/drug effects — Cell Line, Tumor — Diet — Docosahexaenoic Acids/administration & dosage/pharmacology — Female — Interleukin-17/metabolism — Mammary Neoplasms, Experimental/genetics/pathology/prevention & control — Mice — Mice, Inbred BALB C — Mice, Inbred C57BL — Mice, Knockout — Mice, Nude — PPAR gamma/agonists/genetics/metabolism — Promoter Regions, Genetic/genetics — RNA Interference — Reverse Transcriptase Polymerase Chain Reaction — Suppressor of Cytokine Signaling Proteins/genetics/metabolism — Th17 Cells/drug effects/metabolism — Transcriptional Activation — Tumor Burden/drug effects/genetics | |
Identifiers | PMID: 23619236 | |
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Research group | Groupe Pot-Kreis Caroline (931) | |
Citation (ISO format) | BERGER, Hélène et al. SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth. In: Cancer research, 2013, vol. 73, n° 12, p. 3578-90. doi: 10.1158/0008-5472.CAN-12-4018 https://archive-ouverte.unige.ch/unige:33010 |