Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation

Detalhes bibliográficos
Autor(a) principal: Pinheiro, Nathalia Montouro
Data de Publicação: 2020
Outros Autores: Miranda, Cláudia Jeane Claudino de Pontes, Santana, Fernanda Paula Roncon [UNIFESP], Bittencourt-Mernak, Marcia Isabel [UNIFESP], Arantes-Costas, Fernanda Magalhães, Olivo, Clarice Rosa, Perini, Adenir, Festa, Sergio [UNIFESP], Caperuto, Luciana Chagas [UNIFESP], Tiberio, Iolanda de Fátima Lopes Calvo, Prado, Marco Antônio Máximo, Martins, Milton de Arruda, Prado, Vânia Ferreira, Prado, Carla Máximo [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://doi.org/10.1016/j.ejphar.2020.173239
https://repositorio.unifesp.br/handle/11600/61225
Resumo: The cholinergic anti-inflammatory pathway has been shown to regulate lung inflammation and cytokine release in acute models of inflammation, mainly via α7 nicotinic receptor (α7nAChR). We aimed to evaluate the role of endogenous acetylcholine in chronic allergic airway inflammation in mice and the effects of therapeutic nAChR stimulation in this model. We first evaluated lung inflammation and remodeling on knock-down mice with 65% of vesicular acetylcholine transport (VAChT) gene reduction (KDVAChT) and wild-type(WT) controls that were subcutaneously sensitized and then inhaled with ovalbumin(OVA). We then evaluated the effects of PNU-282987(0.5-to-2mg/kg),(α7nAChR agonist) treatment in BALB/c male mice intraperitoneal sensitized and then inhaled with OVA. Another OVA-sensitized-group was treated with PNU-282987 plus Methyllycaconitine (MLA,1 mg/kg, α7nAChR antagonist) to confirm that the effects observed by PNU were due to α7nAChR. We showed that KDVAChT-OVA mice exhibit exacerbated airway inflammation when compared to WT-OVA mice. In BALB/c, PNU-282987 treatment reduced the number of eosinophils in the blood, BAL fluid, and around airways, and also decreased pulmonary levels of IL-4,IL-13,IL-17, and IgE in the serum of OVA-exposed mice. MLA pre-treatment abolished all the effects of PNU-282987. Additionally, we showed that PNU-282987 inhibited STAT3-phosphorylation and reduced SOCS3 expression in the lung. These data indicate that endogenous cholinergic tone is important to control allergic airway inflammation in a murine model. Moreover, α7nAChR is involved in the control of eosinophilic inflammation and airway remodeling, possibly via inhibition of STAT3/SOCS3 pathways. Together these data suggest that cholinergic anti-inflammatory system mainly α7nAChR should be further considered as a therapeutic target in asthma.
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spelling Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammationChronic allergic airway inflammationVesicular acetylcholine transporterα7 nicotinic acetylcholineThe cholinergic anti-inflammatory pathway has been shown to regulate lung inflammation and cytokine release in acute models of inflammation, mainly via α7 nicotinic receptor (α7nAChR). We aimed to evaluate the role of endogenous acetylcholine in chronic allergic airway inflammation in mice and the effects of therapeutic nAChR stimulation in this model. We first evaluated lung inflammation and remodeling on knock-down mice with 65% of vesicular acetylcholine transport (VAChT) gene reduction (KDVAChT) and wild-type(WT) controls that were subcutaneously sensitized and then inhaled with ovalbumin(OVA). We then evaluated the effects of PNU-282987(0.5-to-2mg/kg),(α7nAChR agonist) treatment in BALB/c male mice intraperitoneal sensitized and then inhaled with OVA. Another OVA-sensitized-group was treated with PNU-282987 plus Methyllycaconitine (MLA,1 mg/kg, α7nAChR antagonist) to confirm that the effects observed by PNU were due to α7nAChR. We showed that KDVAChT-OVA mice exhibit exacerbated airway inflammation when compared to WT-OVA mice. In BALB/c, PNU-282987 treatment reduced the number of eosinophils in the blood, BAL fluid, and around airways, and also decreased pulmonary levels of IL-4,IL-13,IL-17, and IgE in the serum of OVA-exposed mice. MLA pre-treatment abolished all the effects of PNU-282987. Additionally, we showed that PNU-282987 inhibited STAT3-phosphorylation and reduced SOCS3 expression in the lung. These data indicate that endogenous cholinergic tone is important to control allergic airway inflammation in a murine model. Moreover, α7nAChR is involved in the control of eosinophilic inflammation and airway remodeling, possibly via inhibition of STAT3/SOCS3 pathways. Together these data suggest that cholinergic anti-inflammatory system mainly α7nAChR should be further considered as a therapeutic target in asthma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 2018/15738-9FAPESP: 08/55359-5FAPESP: 14/25689-4CNPq: 476877/2012-1Elsevierhttp://lattes.cnpq.br/8960401765088965Universidade Federal de São Paulo (UNIFESP)Pinheiro, Nathalia MontouroMiranda, Cláudia Jeane Claudino de PontesSantana, Fernanda Paula Roncon [UNIFESP]Bittencourt-Mernak, Marcia Isabel [UNIFESP]Arantes-Costas, Fernanda MagalhãesOlivo, Clarice RosaPerini, AdenirFesta, Sergio [UNIFESP]Caperuto, Luciana Chagas [UNIFESP]Tiberio, Iolanda de Fátima Lopes CalvoPrado, Marco Antônio MáximoMartins, Milton de ArrudaPrado, Vânia FerreiraPrado, Carla Máximo [UNIFESP]2021-06-25T19:26:25Z2021-06-25T19:26:25Z2020-09-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1016/j.ejphar.2020.173239https://repositorio.unifesp.br/handle/11600/61225engEur J Pharmacolinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T12:39:08Zoai:repositorio.unifesp.br/:11600/61225Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T12:39:08Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
title Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
spellingShingle Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
Pinheiro, Nathalia Montouro
Chronic allergic airway inflammation
Vesicular acetylcholine transporter
α7 nicotinic acetylcholine
title_short Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
title_full Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
title_fullStr Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
title_full_unstemmed Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
title_sort Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
author Pinheiro, Nathalia Montouro
author_facet Pinheiro, Nathalia Montouro
Miranda, Cláudia Jeane Claudino de Pontes
Santana, Fernanda Paula Roncon [UNIFESP]
Bittencourt-Mernak, Marcia Isabel [UNIFESP]
Arantes-Costas, Fernanda Magalhães
Olivo, Clarice Rosa
Perini, Adenir
Festa, Sergio [UNIFESP]
Caperuto, Luciana Chagas [UNIFESP]
Tiberio, Iolanda de Fátima Lopes Calvo
Prado, Marco Antônio Máximo
Martins, Milton de Arruda
Prado, Vânia Ferreira
Prado, Carla Máximo [UNIFESP]
author_role author
author2 Miranda, Cláudia Jeane Claudino de Pontes
Santana, Fernanda Paula Roncon [UNIFESP]
Bittencourt-Mernak, Marcia Isabel [UNIFESP]
Arantes-Costas, Fernanda Magalhães
Olivo, Clarice Rosa
Perini, Adenir
Festa, Sergio [UNIFESP]
Caperuto, Luciana Chagas [UNIFESP]
Tiberio, Iolanda de Fátima Lopes Calvo
Prado, Marco Antônio Máximo
Martins, Milton de Arruda
Prado, Vânia Ferreira
Prado, Carla Máximo [UNIFESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv http://lattes.cnpq.br/8960401765088965
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Pinheiro, Nathalia Montouro
Miranda, Cláudia Jeane Claudino de Pontes
Santana, Fernanda Paula Roncon [UNIFESP]
Bittencourt-Mernak, Marcia Isabel [UNIFESP]
Arantes-Costas, Fernanda Magalhães
Olivo, Clarice Rosa
Perini, Adenir
Festa, Sergio [UNIFESP]
Caperuto, Luciana Chagas [UNIFESP]
Tiberio, Iolanda de Fátima Lopes Calvo
Prado, Marco Antônio Máximo
Martins, Milton de Arruda
Prado, Vânia Ferreira
Prado, Carla Máximo [UNIFESP]
dc.subject.por.fl_str_mv Chronic allergic airway inflammation
Vesicular acetylcholine transporter
α7 nicotinic acetylcholine
topic Chronic allergic airway inflammation
Vesicular acetylcholine transporter
α7 nicotinic acetylcholine
description The cholinergic anti-inflammatory pathway has been shown to regulate lung inflammation and cytokine release in acute models of inflammation, mainly via α7 nicotinic receptor (α7nAChR). We aimed to evaluate the role of endogenous acetylcholine in chronic allergic airway inflammation in mice and the effects of therapeutic nAChR stimulation in this model. We first evaluated lung inflammation and remodeling on knock-down mice with 65% of vesicular acetylcholine transport (VAChT) gene reduction (KDVAChT) and wild-type(WT) controls that were subcutaneously sensitized and then inhaled with ovalbumin(OVA). We then evaluated the effects of PNU-282987(0.5-to-2mg/kg),(α7nAChR agonist) treatment in BALB/c male mice intraperitoneal sensitized and then inhaled with OVA. Another OVA-sensitized-group was treated with PNU-282987 plus Methyllycaconitine (MLA,1 mg/kg, α7nAChR antagonist) to confirm that the effects observed by PNU were due to α7nAChR. We showed that KDVAChT-OVA mice exhibit exacerbated airway inflammation when compared to WT-OVA mice. In BALB/c, PNU-282987 treatment reduced the number of eosinophils in the blood, BAL fluid, and around airways, and also decreased pulmonary levels of IL-4,IL-13,IL-17, and IgE in the serum of OVA-exposed mice. MLA pre-treatment abolished all the effects of PNU-282987. Additionally, we showed that PNU-282987 inhibited STAT3-phosphorylation and reduced SOCS3 expression in the lung. These data indicate that endogenous cholinergic tone is important to control allergic airway inflammation in a murine model. Moreover, α7nAChR is involved in the control of eosinophilic inflammation and airway remodeling, possibly via inhibition of STAT3/SOCS3 pathways. Together these data suggest that cholinergic anti-inflammatory system mainly α7nAChR should be further considered as a therapeutic target in asthma.
publishDate 2020
dc.date.none.fl_str_mv 2020-09-05
2021-06-25T19:26:25Z
2021-06-25T19:26:25Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.1016/j.ejphar.2020.173239
https://repositorio.unifesp.br/handle/11600/61225
url https://doi.org/10.1016/j.ejphar.2020.173239
https://repositorio.unifesp.br/handle/11600/61225
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Eur J Pharmacol
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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