CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation

Autores
Hernangómez, Miriam; Mestre, Leyre; Correa, Fernando Gabriel; Loría, Frida; Mecha, Miriam; Iñigo, Paula M.; Docagne, Fabian; Williams, Richard O.; Borrell, Jorge; Guaza, Carmen
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 CB2 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-1β 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-1β 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.
Fil: Hernangómez, Miriam. Consejo Superior de Investigaciones Cientificas; España
Fil: Mestre, Leyre. Consejo Superior de Investigaciones Cientificas; España
Fil: Correa, Fernando Gabriel. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Loría, Frida. Consejo Superior de Investigaciones Cientificas; España
Fil: Mecha, Miriam. Consejo Superior de Investigaciones Cientificas; España
Fil: Iñigo, Paula M.. Consejo Superior de Investigaciones Cientificas; España
Fil: Docagne, Fabian. Inserm; Francia
Fil: Williams, Richard O.. Imperial College London; Reino Unido
Fil: Borrell, Jorge. Consejo Superior de Investigaciones Cientificas; España
Fil: Guaza, Carmen. Consejo Superior de Investigaciones Cientificas; España
Materia
Endocannabinoids
Cd200 And Cd200r
Il-10 And Neuroinflammation
Tmev And Multiple Sclerosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/17252
Acceder
id CONICETDig_87587fd41da06375ce11403958b48217
oai_identifier_str oai:ri.conicet.gov.ar:11336/17252
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammationHernangómez, MiriamMestre, LeyreCorrea, Fernando GabrielLoría, FridaMecha, MiriamIñigo, Paula M.Docagne, FabianWilliams, Richard O.Borrell, JorgeGuaza, CarmenEndocannabinoidsCd200 And Cd200rIl-10 And NeuroinflammationTmev And Multiple Sclerosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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 CB2 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-1β 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-1β 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.Fil: Hernangómez, Miriam. Consejo Superior de Investigaciones Cientificas; EspañaFil: Mestre, Leyre. Consejo Superior de Investigaciones Cientificas; EspañaFil: Correa, Fernando Gabriel. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Loría, Frida. Consejo Superior de Investigaciones Cientificas; EspañaFil: Mecha, Miriam. Consejo Superior de Investigaciones Cientificas; EspañaFil: Iñigo, Paula M.. Consejo Superior de Investigaciones Cientificas; EspañaFil: Docagne, Fabian. Inserm; FranciaFil: Williams, Richard O.. Imperial College London; Reino UnidoFil: Borrell, Jorge. Consejo Superior de Investigaciones Cientificas; EspañaFil: Guaza, Carmen. Consejo Superior de Investigaciones Cientificas; EspañaWiley2012-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17252Hernangómez, Miriam; Mestre, Leyre; Correa, Fernando Gabriel; Loría, Frida; Mecha, Miriam; et al.; CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation; Wiley; Glia; 60; 9; 9-2012; 1437-14500894-1491enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/glia.22366/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/glia.22366info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:45:24Zoai:ri.conicet.gov.ar:11336/17252instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:45:24.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
title CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
spellingShingle CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
Hernangómez, Miriam
Endocannabinoids
Cd200 And Cd200r
Il-10 And Neuroinflammation
Tmev And Multiple Sclerosis
title_short CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
title_full CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
title_fullStr CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
title_full_unstemmed CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
title_sort CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation
dc.creator.none.fl_str_mv Hernangómez, Miriam
Mestre, Leyre
Correa, Fernando Gabriel
Loría, Frida
Mecha, Miriam
Iñigo, Paula M.
Docagne, Fabian
Williams, Richard O.
Borrell, Jorge
Guaza, Carmen
author Hernangómez, Miriam
author_facet Hernangómez, Miriam
Mestre, Leyre
Correa, Fernando Gabriel
Loría, Frida
Mecha, Miriam
Iñigo, Paula M.
Docagne, Fabian
Williams, Richard O.
Borrell, Jorge
Guaza, Carmen
author_role author
author2 Mestre, Leyre
Correa, Fernando Gabriel
Loría, Frida
Mecha, Miriam
Iñigo, Paula M.
Docagne, Fabian
Williams, Richard O.
Borrell, Jorge
Guaza, Carmen
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endocannabinoids
Cd200 And Cd200r
Il-10 And Neuroinflammation
Tmev And Multiple Sclerosis
topic Endocannabinoids
Cd200 And Cd200r
Il-10 And Neuroinflammation
Tmev And Multiple Sclerosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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 CB2 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-1β 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-1β 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.
Fil: Hernangómez, Miriam. Consejo Superior de Investigaciones Cientificas; España
Fil: Mestre, Leyre. Consejo Superior de Investigaciones Cientificas; España
Fil: Correa, Fernando Gabriel. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Loría, Frida. Consejo Superior de Investigaciones Cientificas; España
Fil: Mecha, Miriam. Consejo Superior de Investigaciones Cientificas; España
Fil: Iñigo, Paula M.. Consejo Superior de Investigaciones Cientificas; España
Fil: Docagne, Fabian. Inserm; Francia
Fil: Williams, Richard O.. Imperial College London; Reino Unido
Fil: Borrell, Jorge. Consejo Superior de Investigaciones Cientificas; España
Fil: Guaza, Carmen. Consejo Superior de Investigaciones Cientificas; España
description 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 CB2 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-1β 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-1β 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/17252
Hernangómez, Miriam; Mestre, Leyre; Correa, Fernando Gabriel; Loría, Frida; Mecha, Miriam; et al.; CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation; Wiley; Glia; 60; 9; 9-2012; 1437-1450
0894-1491
url http://hdl.handle.net/11336/17252
identifier_str_mv Hernangómez, Miriam; Mestre, Leyre; Correa, Fernando Gabriel; Loría, Frida; Mecha, Miriam; et al.; CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation; Wiley; Glia; 60; 9; 9-2012; 1437-1450
0894-1491
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/glia.22366/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/glia.22366
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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