Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide

[Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP r...

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Autores: Bonfill-Teixidor, Ester, Otxoa de Amezaga, Amaia, Font-Nieves, Míriam, Sans-Fons, M. Gloria, Planas, Anna M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/144361
Acceso en línea:http://hdl.handle.net/10261/144361
Access Level:acceso abierto
Palabra clave:PGE2
EP4
EP2
COX-2
Neuroinflammation
Glia
Mice
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oai_identifier_str oai:digital.csic.es:10261/144361
network_acronym_str ES
network_name_str España
repository_id_str
spelling Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharideBonfill-Teixidor, EsterOtxoa de Amezaga, AmaiaFont-Nieves, MíriamSans-Fons, M. GloriaPlanas, Anna M.PGE2EP4EP2COX-2NeuroinflammationGliaMice[Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS.[Methods] Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA. Cells were treated with PGE2, and the effect on LPS-induced expression of TNF-α messenger RNA (mRNA) and protein was studied in the presence or absence of drug antagonists of the four EP receptors. EP receptor expression and the effects of EP2 and EP4 agonists and antagonists were studied at different time points after LPS.[Results] PGE2 production after LPS was COX-2-dependent. PGE2 reduced the glial production of TNF-α after LPS. Microglia expressed higher levels of EP4 and EP2 mRNA than astroglia. Activation of EP4 or EP2 receptors with selective drug agonists attenuated LPS-induced TNF-α in microglia. However, only antagonizing EP4 prevented the PGE2 effect demonstrating that EP4 was the main target of PGE2 in naïve microglia. Moreover, the relative expression of EP receptors changed during the course of classical microglial activation since EP4 expression was strongly depressed while EP2 increased 24 h after LPS and was detected in nuclear/peri-nuclear locations. EP2 regulated the expression of iNOS, NADPH oxidase-2, and vascular endothelial growth factor. NADPH oxidase-2 and iNOS activities require the oxidation of NADPH, and the pentose phosphate pathway is a main source of NADPH. LPS increased the mRNA expression of the rate-limiting enzyme of the pentose pathway glucose-6-phosphate dehydrogenase, and EP2 activity was involved in this effect.[Conclusions] These results show that while selective activation of EP4 or EP2 exerts anti-inflammatory actions, EP4 is the main target of PGE2 in naïve microglia. The level of EP receptor expression changes from naïve to primed microglia where the COX-2/PGE2/EP2 axis modulates important adaptive metabolic changes.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (SAF2014-56279R) and the European Community FP7 (InMiND project no. 278850). EBT had an FPU PhD fellowship of MINECO.Peer reviewedBioMed CentralMinisterio de Economía y Competitividad (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720172017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/144361reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/278850http://dx.doi.org/10.1186/s12974-016-0780-7Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1443612026-05-22T06:33:51Z
dc.title.none.fl_str_mv Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
title Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
spellingShingle Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
Bonfill-Teixidor, Ester
PGE2
EP4
EP2
COX-2
Neuroinflammation
Glia
Mice
title_short Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
title_full Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
title_fullStr Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
title_full_unstemmed Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
title_sort Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide
dc.creator.none.fl_str_mv Bonfill-Teixidor, Ester
Otxoa de Amezaga, Amaia
Font-Nieves, Míriam
Sans-Fons, M. Gloria
Planas, Anna M.
author Bonfill-Teixidor, Ester
author_facet Bonfill-Teixidor, Ester
Otxoa de Amezaga, Amaia
Font-Nieves, Míriam
Sans-Fons, M. Gloria
Planas, Anna M.
author_role author
author2 Otxoa de Amezaga, Amaia
Font-Nieves, Míriam
Sans-Fons, M. Gloria
Planas, Anna M.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv PGE2
EP4
EP2
COX-2
Neuroinflammation
Glia
Mice
topic PGE2
EP4
EP2
COX-2
Neuroinflammation
Glia
Mice
description [Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/144361
url http://hdl.handle.net/10261/144361
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/278850
http://dx.doi.org/10.1186/s12974-016-0780-7
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411399882506240
score 15.811543

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