Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality

Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this wa...

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Autores: Virgili, Noemi, Mancera, Pilar, Chanvillard, C., Wegner, A., Wappenhans, Blanca, Rodríguez Allué, Manuel José, Infante-Duarte, C., Espinosa Parrilla, Juan Francisco, Pugliese, Marco
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/60705
Acceso en línea:https://hdl.handle.net/2445/60705
Access Level:acceso abierto
Palabra clave:Encefalomielitis
Malalties neurodegeneratives
Canals de potassi
Mitocondris
Encephalomyelitis
Neurodegenerative Diseases
Potassium channels
Mitochondria
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spelling Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionalityVirgili, NoemiMancera, PilarChanvillard, C.Wegner, A.Wappenhans, BlancaRodríguez Allué, Manuel JoséInfante-Duarte, C.Espinosa Parrilla, Juan FranciscoPugliese, MarcoEncefalomielitisMalalties neurodegenerativesCanals de potassiMitocondrisEncephalomyelitisNeurodegenerative DiseasesPotassium channelsMitochondriaActivation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect.Springer Verlag2014201520142014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion36 p.application/pdfhttps://hdl.handle.net/2445/60705Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1007/s11481-014-9551-3Journal of Neuroimmune Pharmacology, 2014, vol. 9, p. 558-568http://dx.doi.org/10.1007/s11481-014-9551-3(c) Springer Verlag, 2014info:eu-repo/semantics/openAccessoai:recercat.cat:2445/607052026-05-29T05:05:01Z
dc.title.none.fl_str_mv Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
title Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
spellingShingle Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
Virgili, Noemi
Encefalomielitis
Malalties neurodegeneratives
Canals de potassi
Mitocondris
Encephalomyelitis
Neurodegenerative Diseases
Potassium channels
Mitochondria
title_short Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
title_full Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
title_fullStr Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
title_full_unstemmed Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
title_sort Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
dc.creator.none.fl_str_mv Virgili, Noemi
Mancera, Pilar
Chanvillard, C.
Wegner, A.
Wappenhans, Blanca
Rodríguez Allué, Manuel José
Infante-Duarte, C.
Espinosa Parrilla, Juan Francisco
Pugliese, Marco
author Virgili, Noemi
author_facet Virgili, Noemi
Mancera, Pilar
Chanvillard, C.
Wegner, A.
Wappenhans, Blanca
Rodríguez Allué, Manuel José
Infante-Duarte, C.
Espinosa Parrilla, Juan Francisco
Pugliese, Marco
author_role author
author2 Mancera, Pilar
Chanvillard, C.
Wegner, A.
Wappenhans, Blanca
Rodríguez Allué, Manuel José
Infante-Duarte, C.
Espinosa Parrilla, Juan Francisco
Pugliese, Marco
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Encefalomielitis
Malalties neurodegeneratives
Canals de potassi
Mitocondris
Encephalomyelitis
Neurodegenerative Diseases
Potassium channels
Mitochondria
topic Encefalomielitis
Malalties neurodegeneratives
Canals de potassi
Mitocondris
Encephalomyelitis
Neurodegenerative Diseases
Potassium channels
Mitochondria
description Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014
2014
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/60705
url https://hdl.handle.net/2445/60705
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1007/s11481-014-9551-3
Journal of Neuroimmune Pharmacology, 2014, vol. 9, p. 558-568
http://dx.doi.org/10.1007/s11481-014-9551-3
dc.rights.none.fl_str_mv (c) Springer Verlag, 2014
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Verlag, 2014
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 36 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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