Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells

Autores
Chiappini, Florencia Ana; Baston, Juan Ignacio; Vaccarezza, Maria Agustina; Singla, José Javier; Pontillo, Carolina Andrea; Miret, Noelia Victoria; Farina, Mariana; Meresman, Gabriela Fabiana; Randi, Andrea Silvana
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baston, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vaccarezza, Maria Agustina. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Singla, José Javier. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Miret, Noelia Victoria. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Farina, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Aryl Hydrocarbon Receptor
Cyclooxygenase-2
Endometriosis
Hexachlorobenzene
Metalloproteinases
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/82663
Acceder
id CONICETDig_c4eefde6af652248775d8a850783c8f0
oai_identifier_str oai:ri.conicet.gov.ar:11336/82663
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cellsChiappini, Florencia AnaBaston, Juan IgnacioVaccarezza, Maria AgustinaSingla, José JavierPontillo, Carolina AndreaMiret, Noelia VictoriaFarina, MarianaMeresman, Gabriela FabianaRandi, Andrea SilvanaAryl Hydrocarbon ReceptorCyclooxygenase-2EndometriosisHexachlorobenzeneMetalloproteinaseshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baston, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vaccarezza, Maria Agustina. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Singla, José Javier. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miret, Noelia Victoria. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farina, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPergamon-Elsevier Science Ltd2016-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/82663Chiappini, Florencia Ana; Baston, Juan Ignacio; Vaccarezza, Maria Agustina; Singla, José Javier; Pontillo, Carolina Andrea; et al.; Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 109; 6-2016; 91-1040006-2952CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2016.03.024info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295216300053info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:22Zoai:ri.conicet.gov.ar:11336/82663instacron: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 09:43:22.968CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
title Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
spellingShingle Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
Chiappini, Florencia Ana
Aryl Hydrocarbon Receptor
Cyclooxygenase-2
Endometriosis
Hexachlorobenzene
Metalloproteinases
title_short Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
title_full Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
title_fullStr Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
title_full_unstemmed Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
title_sort Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells
dc.creator.none.fl_str_mv Chiappini, Florencia Ana
Baston, Juan Ignacio
Vaccarezza, Maria Agustina
Singla, José Javier
Pontillo, Carolina Andrea
Miret, Noelia Victoria
Farina, Mariana
Meresman, Gabriela Fabiana
Randi, Andrea Silvana
author Chiappini, Florencia Ana
author_facet Chiappini, Florencia Ana
Baston, Juan Ignacio
Vaccarezza, Maria Agustina
Singla, José Javier
Pontillo, Carolina Andrea
Miret, Noelia Victoria
Farina, Mariana
Meresman, Gabriela Fabiana
Randi, Andrea Silvana
author_role author
author2 Baston, Juan Ignacio
Vaccarezza, Maria Agustina
Singla, José Javier
Pontillo, Carolina Andrea
Miret, Noelia Victoria
Farina, Mariana
Meresman, Gabriela Fabiana
Randi, Andrea Silvana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aryl Hydrocarbon Receptor
Cyclooxygenase-2
Endometriosis
Hexachlorobenzene
Metalloproteinases
topic Aryl Hydrocarbon Receptor
Cyclooxygenase-2
Endometriosis
Hexachlorobenzene
Metalloproteinases
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baston, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vaccarezza, Maria Agustina. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Singla, José Javier. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Miret, Noelia Victoria. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Farina, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.
publishDate 2016
dc.date.none.fl_str_mv 2016-06
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/11336/82663
Chiappini, Florencia Ana; Baston, Juan Ignacio; Vaccarezza, Maria Agustina; Singla, José Javier; Pontillo, Carolina Andrea; et al.; Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 109; 6-2016; 91-104
0006-2952
CONICET Digital
CONICET
url http://hdl.handle.net/11336/82663
identifier_str_mv Chiappini, Florencia Ana; Baston, Juan Ignacio; Vaccarezza, Maria Agustina; Singla, José Javier; Pontillo, Carolina Andrea; et al.; Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 109; 6-2016; 91-104
0006-2952
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2016.03.024
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295216300053
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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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