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CD200R1 and CD200 expression are regulated by PPAR-γ in activated glial cells

Authors

  • Guido Dentesano,

    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Joan Serratosa,

    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Josep M. Tusell,

    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Pol Ramón,

    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Tony Valente,

    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Josep Saura,

    1. Biochemistry and Molecular Biology Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
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  • Carme Solà

    Corresponding author
    1. Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain
    • Address correspondence to Carme Solà, Department Cerebral Ischemia and Neurodegeneration, IIBB-CSIC, C/Rosselló 161, 6th Floor, E-08036 Barcelona, Spain. E-mail: carme.sola@iibb.csic.es

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Abstract

The mechanisms that control microglial activation are of interest, since neuroinflammation, which involves reactive microglia, may be an additional target in the search for therapeutic strategies to treat neurodegenerative diseases. Neuron-microglia interaction through contact-dependent or independent mechanisms is involved in the regulation of the microglial phenotype in both physiological and pathological conditions. The interaction between CD200, which is mainly present in neurons but also in astrocytes, and CD200R1, which is mainly present in microglia, is one of the mechanisms involved in keeping the microglial proinflammatory phenotype under control in physiological conditions. Alterations in the expression of CD200 and CD200R1 have been described in neurodegenerative diseases, but little is known about the mechanism of regulation of these proteins under physiological or pathological conditions. The aim of this work was to study the modulation of CD200 and CD200R1 expression by peroxisome proliferator-activated receptor gamma (PPAR-γ), a transcription factor involved in the control of the inflammatory response. Mouse primary neuronal and glial cultures and neuron-microglia cocultures were treated with the PPAR-γ endogenous ligand 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) in the presence and absence of lipopolysaccharide plus interferon-γ (LPS/IFN-γ)-induced glial activation. We show that 15d-PGJ2 inhibits the pro-inflammatory response and prevents both CD200R1 downregulation and CD200 upregulation in reactive glial cells. In addition, 15d-PGJ2 abrogates reactive-microglia induced neurotoxicity in neuron-microglia cultures through a CD200-CD200R1 dependent mechanism. These results suggest that PPAR-γ modulates CD200 and CD200R1 gene expression and that CD200-CD200R1 interaction is involved in the anti-inflammatory and neuroprotective action of PPAR-γ agonists. GLIA 2014;62:982–998

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