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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/251028
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:34:22Zoai: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:34982025-09-29 09:34:22.645CONICET 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 |
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publishedVersion |
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conferenceObject |
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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 |
dc.relation.none.fl_str_mv |
https://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/ |
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Internacional |
dc.publisher.none.fl_str_mv |
Sociedad de Bioquímica y Biología Molecular de Chile |
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Sociedad de Bioquímica y Biología Molecular de Chile |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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