CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation.
Glia
; 60(9): 1437-50, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22653796
ABSTRACT
The endocannabinoid anandamide (AEA) is released by macrophages and microglia on pathological neuroinflammatory conditions such as multiple sclerosis (MS). CD200 is a membrane glycoprotein expressed in neurons that suppresses immune activity via its receptor (CD200R) mainly located in macrophages/microglia. CD200-CD200R interactions contribute to the brain immune privileged status. In this study, we show that AEA protects neurons from microglia-induced neurotoxicity via CD200-CD200R interaction. AEA increases the expression of CD200R1 in LPS/IFN-γ activated microglia through the activation of CB(2) receptors. The neuroprotective effect of AEA disappears when microglial cells derive from CD200R1(-/-) mice. We also show that engagement of CD200R1 by CD200Fc decreased the production of the proinflammatory cytokines IL-1ß and IL-6, but increased IL-10 in activated microglia. In the chronic phases of Theiler's virus-induced demyelinating disease (TMEV-IDD) the expression of CD200 and CD200R1 was reduced in the spinal cord. AEA-treated animals up-regulated the expression of CD200 and CD200R1, restoring levels found in sham animals together with increased expression of IL-10 and reduced expression of IL-1ß and IL-6. Treated animals also improved their motor behavior. Because AEA up-regulated the expression of CD200R1 in microglia, but failed to enhance CD200 in neurons we suggest that AEA-induced up-regulation of CD200 in TMEV-IDD is likely due to IL-10 as this cytokine increases CD200 in neurons. Our findings provide a new mechanism of action of AEA to limit immune response in the inflamed brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Antígenos CD
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Ácidos Araquidônicos
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Receptores de Superfície Celular
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Fármacos Neuroprotetores
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Endocanabinoides
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Alcamidas Poli-Insaturadas
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Inflamação
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Antígenos de Superfície
Limite:
Animals
Idioma:
En
Revista:
Glia
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha