期刊
GLIA
卷 62, 期 6, 页码 982-998出版社
WILEY
DOI: 10.1002/glia.22656
关键词
astroglia; microglia; neuroinflammation; neuroprotection; in vitro; anti-inflammatory
资金
- La Marato de TV3 [110530]
- Instituto de Salud Carlos III
- Spain-FEDER funds
- European Union [PI10/378, PI12/00709]
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-gamma), 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-gamma endogenous ligand 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)) in the presence and absence of lipopolysaccharide plus interferon-gamma (LPS/IFN-gamma)-induced glial activation. We show that 15d-PGJ(2) inhibits the pro-inflammatory response and prevents both CD200R1 downregulation and CD200 upregulation in reactive glial cells. In addition, 15d-PGJ(2) abrogates reactive-microglia induced neurotoxicity in neuron-microglia cultures through a CD200-CD200R1 dependent mechanism. These results suggest that PPAR-gamma modulates CD200 and CD200R1 gene expression and that CD200-CD200R1 interaction is involved in the anti-inflammatory and neuroprotective action of PPAR-gamma agonists. GLIA 2014;62:982-998
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