Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis

Autores
Theas, Maria Susana; Rival, C.; Jarazo Dietrich, Sabrina Soledad; Jacobo, Patricia Verónica; Guazzone, Vanesa Anabella; Lustig, Livia
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-a in GC apoptosis. METHODS AND RESULTS: Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling,TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-a content (enzymelinked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-a blocker (Etanercept). Moreover, TNF-a in vitro induced GC apoptosis. TNF-a expression (by immunofluorescence) was observed in testicular (ED2+) and non-resident (ED1+) macrophages, the percentage of TNF-a+ macrophages being similar in focal and severe orchitis. CONCLUSIONS: Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-a is a relevant cytokine involved in testicular damage during severe orchitis.
Fil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rival, C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Materia
autoimmune orchitis
testis
macrophages
tumour necrosis factor-a; apoptosis
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:11336/111325
Acceder
id CONICETDig_0af346f1e93edd1b5e23c1434422922a
oai_identifier_str oai:ri.conicet.gov.ar:11336/111325
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitisTheas, Maria SusanaRival, C.Jarazo Dietrich, Sabrina SoledadJacobo, Patricia VerónicaGuazzone, Vanesa AnabellaLustig, Liviaautoimmune orchitistestismacrophagestumour necrosis factor-a; apoptosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-a in GC apoptosis. METHODS AND RESULTS: Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling,TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-a content (enzymelinked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-a blocker (Etanercept). Moreover, TNF-a in vitro induced GC apoptosis. TNF-a expression (by immunofluorescence) was observed in testicular (ED2+) and non-resident (ED1+) macrophages, the percentage of TNF-a+ macrophages being similar in focal and severe orchitis. CONCLUSIONS: Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-a is a relevant cytokine involved in testicular damage during severe orchitis.Fil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Rival, C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; ArgentinaFil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; ArgentinaFil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; ArgentinaOxford University Press2008-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/111325Theas, Maria Susana; Rival, C.; Jarazo Dietrich, Sabrina Soledad; Jacobo, Patricia Verónica; Guazzone, Vanesa Anabella; et al.; Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis; Oxford University Press; Human Reproduction; 23; 8; 5-2008; 1865-18720268-1161CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://humrep.oxfordjournals.org/content/23/8/1865.longinfo:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/den240info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:38Zoai:ri.conicet.gov.ar:11336/111325instacron: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:34982025-09-03 09:45:40.454CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
title Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
spellingShingle Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
Theas, Maria Susana
autoimmune orchitis
testis
macrophages
tumour necrosis factor-a; apoptosis
title_short Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
title_full Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
title_fullStr Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
title_full_unstemmed Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
title_sort Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis
dc.creator.none.fl_str_mv Theas, Maria Susana
Rival, C.
Jarazo Dietrich, Sabrina Soledad
Jacobo, Patricia Verónica
Guazzone, Vanesa Anabella
Lustig, Livia
author Theas, Maria Susana
author_facet Theas, Maria Susana
Rival, C.
Jarazo Dietrich, Sabrina Soledad
Jacobo, Patricia Verónica
Guazzone, Vanesa Anabella
Lustig, Livia
author_role author
author2 Rival, C.
Jarazo Dietrich, Sabrina Soledad
Jacobo, Patricia Verónica
Guazzone, Vanesa Anabella
Lustig, Livia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv autoimmune orchitis
testis
macrophages
tumour necrosis factor-a; apoptosis
topic autoimmune orchitis
testis
macrophages
tumour necrosis factor-a; apoptosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-a in GC apoptosis. METHODS AND RESULTS: Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling,TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-a content (enzymelinked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-a blocker (Etanercept). Moreover, TNF-a in vitro induced GC apoptosis. TNF-a expression (by immunofluorescence) was observed in testicular (ED2+) and non-resident (ED1+) macrophages, the percentage of TNF-a+ macrophages being similar in focal and severe orchitis. CONCLUSIONS: Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-a is a relevant cytokine involved in testicular damage during severe orchitis.
Fil: Theas, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rival, C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Jarazo Dietrich, Sabrina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
Fil: Jacobo, Patricia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina
description BACKGROUND: Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-a in GC apoptosis. METHODS AND RESULTS: Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling,TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-a content (enzymelinked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-a blocker (Etanercept). Moreover, TNF-a in vitro induced GC apoptosis. TNF-a expression (by immunofluorescence) was observed in testicular (ED2+) and non-resident (ED1+) macrophages, the percentage of TNF-a+ macrophages being similar in focal and severe orchitis. CONCLUSIONS: Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-a is a relevant cytokine involved in testicular damage during severe orchitis.
publishDate 2008
dc.date.none.fl_str_mv 2008-05
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/11336/111325
Theas, Maria Susana; Rival, C.; Jarazo Dietrich, Sabrina Soledad; Jacobo, Patricia Verónica; Guazzone, Vanesa Anabella; et al.; Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis; Oxford University Press; Human Reproduction; 23; 8; 5-2008; 1865-1872
0268-1161
CONICET Digital
CONICET
url http://hdl.handle.net/11336/111325
identifier_str_mv Theas, Maria Susana; Rival, C.; Jarazo Dietrich, Sabrina Soledad; Jacobo, Patricia Verónica; Guazzone, Vanesa Anabella; et al.; Tumour necrosis factor-  released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis; Oxford University Press; Human Reproduction; 23; 8; 5-2008; 1865-1872
0268-1161
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://humrep.oxfordjournals.org/content/23/8/1865.long
info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/den240
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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 13.13397

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