1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism

Autores
Tapia, Cinthya Mariela; Suares, Alejandra Carolina; González Pardo, María Verónica
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
KS-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) is the key molecule in Kaposi?s sarcoma. vGPCR continuous expression and activity are required for tumor preservation. We have previously shown 1α,25(OH)2D3 antineoplastic effect in endothelial cells expressing vGPCR by negative modulation of NF-κB pro-inflammatory pathway. In this work, we further explored 1α,25(OH)2D3 anti-inflammatory mechanism of action. For this purpose, the activity and expression of COX-2, head enzyme to produce prostaglandins (PGs), 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) which inactivates PGE2 and the four different PGs receptors (EP1-4) were analyzed after 1α,25(OH)2D3 treatment. MTS and proliferation assays were used to determine cell metabolism and proliferation before and after 1α,25(OH)2D3 (10 nM); ATK (10-20 µM), PLA2 inhibitor; and Celecoxib (10-20 µM), COX-2 selective inhibitor. Morphological changes and cell number decrease were observed in a dose-dependent manner. Contrary to what was expected, COX-2 gene expression increased after different times of 1α,25(OH)2D3 (10 nM) treatment. This increment was found to be VDR dependent, using a stable VDR knock-down cell line vGPCR-shVDR. However, when COX-2 expression was higher (up to 24 h), its peroxidase activity was lower. Finally, after longer 1α,25(OH)2D3-treatment periods (12 h or more) 15-PGDH and EP1 and EP2 low affinity receptors gene expression was elevated counter to EP3 and EP4 high affinity receptors, which gene expression was found decayed. All together, these results suggest that despite 1α,25(OH)2D3 enhances vGPCR-induced endothelial inflammation due to COX-2 increased expression, it also behaves as an attenuator of inflammation. Supported by grants from CONICET 11220150100057CO and FONCyT PICT-2013-0552 to Veronica Gonzalez-Pardo.
Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
SISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular Medicine
San Carlos de Bariloche
Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas
Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación
Materia
VITAMIN D
INFLAMMATION
COX-2
vGPCR CELLS
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:11336/251028
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanismTapia, Cinthya MarielaSuares, Alejandra CarolinaGonzález Pardo, María VerónicaVITAMIN DINFLAMMATIONCOX-2vGPCR CELLShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1KS-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) is the key molecule in Kaposi?s sarcoma. vGPCR continuous expression and activity are required for tumor preservation. We have previously shown 1α,25(OH)2D3 antineoplastic effect in endothelial cells expressing vGPCR by negative modulation of NF-κB pro-inflammatory pathway. In this work, we further explored 1α,25(OH)2D3 anti-inflammatory mechanism of action. For this purpose, the activity and expression of COX-2, head enzyme to produce prostaglandins (PGs), 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) which inactivates PGE2 and the four different PGs receptors (EP1-4) were analyzed after 1α,25(OH)2D3 treatment. MTS and proliferation assays were used to determine cell metabolism and proliferation before and after 1α,25(OH)2D3 (10 nM); ATK (10-20 µM), PLA2 inhibitor; and Celecoxib (10-20 µM), COX-2 selective inhibitor. Morphological changes and cell number decrease were observed in a dose-dependent manner. Contrary to what was expected, COX-2 gene expression increased after different times of 1α,25(OH)2D3 (10 nM) treatment. This increment was found to be VDR dependent, using a stable VDR knock-down cell line vGPCR-shVDR. However, when COX-2 expression was higher (up to 24 h), its peroxidase activity was lower. Finally, after longer 1α,25(OH)2D3-treatment periods (12 h or more) 15-PGDH and EP1 and EP2 low affinity receptors gene expression was elevated counter to EP3 and EP4 high affinity receptors, which gene expression was found decayed. All together, these results suggest that despite 1α,25(OH)2D3 enhances vGPCR-induced endothelial inflammation due to COX-2 increased expression, it also behaves as an attenuator of inflammation. Supported by grants from CONICET 11220150100057CO and FONCyT PICT-2013-0552 to Veronica Gonzalez-Pardo.Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaSISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular MedicineSan Carlos de BarilocheArgentinaConsejo Nacional de Investigaciones Científicas y TécnicasAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la InnovaciónSociedad de Bioquímica y Biología Molecular de ChileDavis, Roger2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2510281α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism; SISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular Medicine; San Carlos de Bariloche; Argentina; 2018; 73-73CONICET DigitalCONICETenghttps://www.sbbmch.cl/the-fourth-south-american-symposium-in-signal-transduction-and-molecular-medicine/info:eu-repo/semantics/altIdentifier/url/https://www.sbbmch.cl/the-fourth-south-american-symposium-in-signal-transduction-and-molecular-medicine/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:22:43Zoai:ri.conicet.gov.ar:11336/251028instacron: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:34982025-10-15 14:22:44.104CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
title 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
spellingShingle 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
Tapia, Cinthya Mariela
VITAMIN D
INFLAMMATION
COX-2
vGPCR CELLS
title_short 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
title_full 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
title_fullStr 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
title_full_unstemmed 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
title_sort 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism
dc.creator.none.fl_str_mv Tapia, Cinthya Mariela
Suares, Alejandra Carolina
González Pardo, María Verónica
author Tapia, Cinthya Mariela
author_facet Tapia, Cinthya Mariela
Suares, Alejandra Carolina
González Pardo, María Verónica
author_role author
author2 Suares, Alejandra Carolina
González Pardo, María Verónica
author2_role author
author
dc.contributor.none.fl_str_mv Davis, Roger
dc.subject.none.fl_str_mv VITAMIN D
INFLAMMATION
COX-2
vGPCR CELLS
topic VITAMIN D
INFLAMMATION
COX-2
vGPCR CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv KS-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) is the key molecule in Kaposi?s sarcoma. vGPCR continuous expression and activity are required for tumor preservation. We have previously shown 1α,25(OH)2D3 antineoplastic effect in endothelial cells expressing vGPCR by negative modulation of NF-κB pro-inflammatory pathway. In this work, we further explored 1α,25(OH)2D3 anti-inflammatory mechanism of action. For this purpose, the activity and expression of COX-2, head enzyme to produce prostaglandins (PGs), 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) which inactivates PGE2 and the four different PGs receptors (EP1-4) were analyzed after 1α,25(OH)2D3 treatment. MTS and proliferation assays were used to determine cell metabolism and proliferation before and after 1α,25(OH)2D3 (10 nM); ATK (10-20 µM), PLA2 inhibitor; and Celecoxib (10-20 µM), COX-2 selective inhibitor. Morphological changes and cell number decrease were observed in a dose-dependent manner. Contrary to what was expected, COX-2 gene expression increased after different times of 1α,25(OH)2D3 (10 nM) treatment. This increment was found to be VDR dependent, using a stable VDR knock-down cell line vGPCR-shVDR. However, when COX-2 expression was higher (up to 24 h), its peroxidase activity was lower. Finally, after longer 1α,25(OH)2D3-treatment periods (12 h or more) 15-PGDH and EP1 and EP2 low affinity receptors gene expression was elevated counter to EP3 and EP4 high affinity receptors, which gene expression was found decayed. All together, these results suggest that despite 1α,25(OH)2D3 enhances vGPCR-induced endothelial inflammation due to COX-2 increased expression, it also behaves as an attenuator of inflammation. Supported by grants from CONICET 11220150100057CO and FONCyT PICT-2013-0552 to Veronica Gonzalez-Pardo.
Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
SISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular Medicine
San Carlos de Bariloche
Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas
Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación
description KS-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) is the key molecule in Kaposi?s sarcoma. vGPCR continuous expression and activity are required for tumor preservation. We have previously shown 1α,25(OH)2D3 antineoplastic effect in endothelial cells expressing vGPCR by negative modulation of NF-κB pro-inflammatory pathway. In this work, we further explored 1α,25(OH)2D3 anti-inflammatory mechanism of action. For this purpose, the activity and expression of COX-2, head enzyme to produce prostaglandins (PGs), 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) which inactivates PGE2 and the four different PGs receptors (EP1-4) were analyzed after 1α,25(OH)2D3 treatment. MTS and proliferation assays were used to determine cell metabolism and proliferation before and after 1α,25(OH)2D3 (10 nM); ATK (10-20 µM), PLA2 inhibitor; and Celecoxib (10-20 µM), COX-2 selective inhibitor. Morphological changes and cell number decrease were observed in a dose-dependent manner. Contrary to what was expected, COX-2 gene expression increased after different times of 1α,25(OH)2D3 (10 nM) treatment. This increment was found to be VDR dependent, using a stable VDR knock-down cell line vGPCR-shVDR. However, when COX-2 expression was higher (up to 24 h), its peroxidase activity was lower. Finally, after longer 1α,25(OH)2D3-treatment periods (12 h or more) 15-PGDH and EP1 and EP2 low affinity receptors gene expression was elevated counter to EP3 and EP4 high affinity receptors, which gene expression was found decayed. All together, these results suggest that despite 1α,25(OH)2D3 enhances vGPCR-induced endothelial inflammation due to COX-2 increased expression, it also behaves as an attenuator of inflammation. Supported by grants from CONICET 11220150100057CO and FONCyT PICT-2013-0552 to Veronica Gonzalez-Pardo.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/251028
1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism; SISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular Medicine; San Carlos de Bariloche; Argentina; 2018; 73-73
CONICET Digital
CONICET
url http://hdl.handle.net/11336/251028
identifier_str_mv 1α,25(oh)2d3 modulates inflammation in endothelial cells transformed by vgpcr as part of its antineoplastic mechanism; SISTAM 2018: The Fourth South American Symposium in Signal Transduction and Molecular Medicine; San Carlos de Bariloche; Argentina; 2018; 73-73
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.sbbmch.cl/the-fourth-south-american-symposium-in-signal-transduction-and-molecular-medicine/
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad de Bioquímica y Biología Molecular de Chile
publisher.none.fl_str_mv Sociedad de Bioquímica y Biología Molecular de Chile
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