Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway

Autores
Astudillo, Alma M.; Rodríguez, Juan Pablo; Guijas, Carlos; Rubio, Julio M.; Balboa, María A.; Balsinde Rodríguez, Jesús
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2 α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase‐1 (COX‐1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosanstimulation strongly induced the hydrolysis of AA‐containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine‐containing glycerophospholipids remained constant or slightly increased. Double‐labeling experiments with 3H‐ and 14C‐labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared tocontribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX‐1‐derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor‐α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.
Fil: Astudillo, Alma M.. Universidad de Valladolid; España
Fil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Guijas, Carlos. Universidad de Valladolid; España
Fil: Rubio, Julio M.. Universidad de Valladolid; España
Fil: Balboa, María A.. Universidad de Valladolid; España
Fil: Balsinde Rodríguez, Jesús. Universidad de Valladolid; España
Materia
ARACHIDONIC ACID
EICOSANOIDS;
PHOSPHOLIPID REMODELING
PHOSPHOLIPASE A2
INFLAMMATION;
MONOCYTES/MACROPHAGES COPYRIGHT:
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/157423
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/157423
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 PathwayAstudillo, Alma M.Rodríguez, Juan PabloGuijas, CarlosRubio, Julio M.Balboa, María A.Balsinde Rodríguez, JesúsARACHIDONIC ACIDEICOSANOIDS;PHOSPHOLIPID REMODELINGPHOSPHOLIPASE A2INFLAMMATION;MONOCYTES/MACROPHAGES COPYRIGHT:https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2 α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase‐1 (COX‐1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosanstimulation strongly induced the hydrolysis of AA‐containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine‐containing glycerophospholipids remained constant or slightly increased. Double‐labeling experiments with 3H‐ and 14C‐labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared tocontribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX‐1‐derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor‐α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.Fil: Astudillo, Alma M.. Universidad de Valladolid; EspañaFil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Guijas, Carlos. Universidad de Valladolid; EspañaFil: Rubio, Julio M.. Universidad de Valladolid; EspañaFil: Balboa, María A.. Universidad de Valladolid; EspañaFil: Balsinde Rodríguez, Jesús. Universidad de Valladolid; EspañaMDPI2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/157423Astudillo, Alma M.; Rodríguez, Juan Pablo; Guijas, Carlos; Rubio, Julio M.; Balboa, María A.; et al.; Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway; MDPI; Cells; 10; 2; 2-2021; 1-152073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/10/2/447info:eu-repo/semantics/altIdentifier/doi/10.3390/cells10020447info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:57:19Zoai:ri.conicet.gov.ar:11336/157423instacron: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:34982025-10-22 11:57:20.059CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
title Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
spellingShingle Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
Astudillo, Alma M.
ARACHIDONIC ACID
EICOSANOIDS;
PHOSPHOLIPID REMODELING
PHOSPHOLIPASE A2
INFLAMMATION;
MONOCYTES/MACROPHAGES COPYRIGHT:
title_short Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
title_full Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
title_fullStr Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
title_full_unstemmed Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
title_sort Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway
dc.creator.none.fl_str_mv Astudillo, Alma M.
Rodríguez, Juan Pablo
Guijas, Carlos
Rubio, Julio M.
Balboa, María A.
Balsinde Rodríguez, Jesús
author Astudillo, Alma M.
author_facet Astudillo, Alma M.
Rodríguez, Juan Pablo
Guijas, Carlos
Rubio, Julio M.
Balboa, María A.
Balsinde Rodríguez, Jesús
author_role author
author2 Rodríguez, Juan Pablo
Guijas, Carlos
Rubio, Julio M.
Balboa, María A.
Balsinde Rodríguez, Jesús
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ARACHIDONIC ACID
EICOSANOIDS;
PHOSPHOLIPID REMODELING
PHOSPHOLIPASE A2
INFLAMMATION;
MONOCYTES/MACROPHAGES COPYRIGHT:
topic ARACHIDONIC ACID
EICOSANOIDS;
PHOSPHOLIPID REMODELING
PHOSPHOLIPASE A2
INFLAMMATION;
MONOCYTES/MACROPHAGES COPYRIGHT:
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2 α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase‐1 (COX‐1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosanstimulation strongly induced the hydrolysis of AA‐containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine‐containing glycerophospholipids remained constant or slightly increased. Double‐labeling experiments with 3H‐ and 14C‐labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared tocontribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX‐1‐derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor‐α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.
Fil: Astudillo, Alma M.. Universidad de Valladolid; España
Fil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Guijas, Carlos. Universidad de Valladolid; España
Fil: Rubio, Julio M.. Universidad de Valladolid; España
Fil: Balboa, María A.. Universidad de Valladolid; España
Fil: Balsinde Rodríguez, Jesús. Universidad de Valladolid; España
description Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2 α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase‐1 (COX‐1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosanstimulation strongly induced the hydrolysis of AA‐containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine‐containing glycerophospholipids remained constant or slightly increased. Double‐labeling experiments with 3H‐ and 14C‐labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared tocontribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX‐1‐derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor‐α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.
publishDate 2021
dc.date.none.fl_str_mv 2021-02
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/11336/157423
Astudillo, Alma M.; Rodríguez, Juan Pablo; Guijas, Carlos; Rubio, Julio M.; Balboa, María A.; et al.; Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway; MDPI; Cells; 10; 2; 2-2021; 1-15
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/157423
identifier_str_mv Astudillo, Alma M.; Rodríguez, Juan Pablo; Guijas, Carlos; Rubio, Julio M.; Balboa, María A.; et al.; Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway; MDPI; Cells; 10; 2; 2-2021; 1-15
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/10/2/447
info:eu-repo/semantics/altIdentifier/doi/10.3390/cells10020447
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 12.982451

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