Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β

Cardiac fibroblasts (CFs) undergo senescence in reaction to different stressors, leading to a poor prognosis of cardiac disease. Doxorubicin (Doxo) is an antineoplastic drug with strong cardiotoxic effects, which induces IL-1β secretion and thus, triggers a potent pro-inflammatory response. Doxo ind...

Descripción completa

Detalles Bibliográficos
Autores: Espitia Corredor, Jenaro A., Shamoon, Licia, Olivares Silva, Francisco, Rimassa Taré, Constanza, Muñoz Rodríguez, Claudia, Espinoza Pérez, Claudio, Sánchez Ferrer, Carlos Félix, Peiró Vallejo, M. Concepción, Díaz Araya, Guillermo
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/704011
Acceso en línea:http://hdl.handle.net/10486/704011
https://dx.doi.org/10.1016/j.bbadis.2022.166525
Access Level:acceso abierto
Palabra clave:Cardiac fibroblasts
Doxorubicin
Interleukin-1β
Resolvin E1
Senescence
Farmacia
id ES_c8517ea265d19bcd6a905654099cece5
oai_identifier_str oai:repositorio.uam.es:10486/704011
network_acronym_str ES
network_name_str España
repository_id_str
spelling Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1βEspitia Corredor, Jenaro A.Shamoon, LiciaOlivares Silva, FranciscoRimassa Taré, ConstanzaMuñoz Rodríguez, ClaudiaEspinoza Pérez, ClaudioSánchez Ferrer, Carlos FélixPeiró Vallejo, M. ConcepciónDíaz Araya, GuillermoCardiac fibroblastsDoxorubicinInterleukin-1βResolvin E1SenescenceFarmaciaCardiac fibroblasts (CFs) undergo senescence in reaction to different stressors, leading to a poor prognosis of cardiac disease. Doxorubicin (Doxo) is an antineoplastic drug with strong cardiotoxic effects, which induces IL-1β secretion and thus, triggers a potent pro-inflammatory response. Doxo induces CFs senescence; however, the mechanisms are not fully understood. Different pharmacological strategies have been used to eliminate senescent cells by inducing their apoptosis or modifying their secretome. However, Resolvin E1 (RvE1), a lipid derivative resolutive mediator with potent anti-inflammatory effects has not been used before to prevent CFs senescence. CFs were isolated from adult male C57BL/6J mice and subsequently stimulated with Doxo, in the presence or absence of RvE1. Senescence-associated β-galactosidase activity (SA-β-gal), γ-H2A.X, p53, p21, and senescence-associated secretory phenotype (SASP) were evaluated. The involvement of the NLRP3 inflammasome/interleukin-1 receptor (IL-1R) signaling pathway on CFs senescence was studied using an NLRP3 inhibitor (MCC950) and an endogenous IL-1R antagonist (IR1A). Doxo is able to trigger CFs senescence, as evidenced by an increase of γ-H2A.X, p53, p21, and SA-β-gal, and changes in the SASP profile. These Doxo effects were prevented by RvE1. Doxo triggers IL-1β secretion, which was dependent on NLRP3 activation. Doxo-induced CFs senescence was partially blocked by MCC950 and IR1A. In addition, IL-1β also triggered CFs senescence, as evidenced by the increase of γ-H2A.X, p53, p21, SA-β-gal activity, and SASP. All these effects were also prevented by RvE1 treatment. Conclusion: These data show the anti-senescent role of RvE1 in Doxo-induced CFs senescence, which could be mediated by reducing IL-1β secretion.This study was supported by PID2020-115590RB-100/AEI/ 10.13039/501100011033 and FONDECYT 1210627 to C.P., C.F.S.F., and G.D.A., respectively. L.S. and J.A.E.C. are the recipients of FPI Universidad Autonoma ´ de Madrid (SFPI/2020-00053) and Beca Doctorado Nacional Ano ˜ 2017 ANID (21170233) fellowships, respectivelyElsevier20222022-08-18research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/704011https://dx.doi.org/10.1016/j.bbadis.2022.166525reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7040112026-06-23T12:46:27Z
dc.title.none.fl_str_mv Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
title Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
spellingShingle Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
Espitia Corredor, Jenaro A.
Cardiac fibroblasts
Doxorubicin
Interleukin-1β
Resolvin E1
Senescence
Farmacia
title_short Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
title_full Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
title_fullStr Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
title_full_unstemmed Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
title_sort Resolvin E1 attenuates doxorubicin-induced cardiac fibroblast senescence: A key role for IL-1β
dc.creator.none.fl_str_mv Espitia Corredor, Jenaro A.
Shamoon, Licia
Olivares Silva, Francisco
Rimassa Taré, Constanza
Muñoz Rodríguez, Claudia
Espinoza Pérez, Claudio
Sánchez Ferrer, Carlos Félix
Peiró Vallejo, M. Concepción
Díaz Araya, Guillermo
author Espitia Corredor, Jenaro A.
author_facet Espitia Corredor, Jenaro A.
Shamoon, Licia
Olivares Silva, Francisco
Rimassa Taré, Constanza
Muñoz Rodríguez, Claudia
Espinoza Pérez, Claudio
Sánchez Ferrer, Carlos Félix
Peiró Vallejo, M. Concepción
Díaz Araya, Guillermo
author_role author
author2 Shamoon, Licia
Olivares Silva, Francisco
Rimassa Taré, Constanza
Muñoz Rodríguez, Claudia
Espinoza Pérez, Claudio
Sánchez Ferrer, Carlos Félix
Peiró Vallejo, M. Concepción
Díaz Araya, Guillermo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cardiac fibroblasts
Doxorubicin
Interleukin-1β
Resolvin E1
Senescence
Farmacia
topic Cardiac fibroblasts
Doxorubicin
Interleukin-1β
Resolvin E1
Senescence
Farmacia
description Cardiac fibroblasts (CFs) undergo senescence in reaction to different stressors, leading to a poor prognosis of cardiac disease. Doxorubicin (Doxo) is an antineoplastic drug with strong cardiotoxic effects, which induces IL-1β secretion and thus, triggers a potent pro-inflammatory response. Doxo induces CFs senescence; however, the mechanisms are not fully understood. Different pharmacological strategies have been used to eliminate senescent cells by inducing their apoptosis or modifying their secretome. However, Resolvin E1 (RvE1), a lipid derivative resolutive mediator with potent anti-inflammatory effects has not been used before to prevent CFs senescence. CFs were isolated from adult male C57BL/6J mice and subsequently stimulated with Doxo, in the presence or absence of RvE1. Senescence-associated β-galactosidase activity (SA-β-gal), γ-H2A.X, p53, p21, and senescence-associated secretory phenotype (SASP) were evaluated. The involvement of the NLRP3 inflammasome/interleukin-1 receptor (IL-1R) signaling pathway on CFs senescence was studied using an NLRP3 inhibitor (MCC950) and an endogenous IL-1R antagonist (IR1A). Doxo is able to trigger CFs senescence, as evidenced by an increase of γ-H2A.X, p53, p21, and SA-β-gal, and changes in the SASP profile. These Doxo effects were prevented by RvE1. Doxo triggers IL-1β secretion, which was dependent on NLRP3 activation. Doxo-induced CFs senescence was partially blocked by MCC950 and IR1A. In addition, IL-1β also triggered CFs senescence, as evidenced by the increase of γ-H2A.X, p53, p21, SA-β-gal activity, and SASP. All these effects were also prevented by RvE1 treatment. Conclusion: These data show the anti-senescent role of RvE1 in Doxo-induced CFs senescence, which could be mediated by reducing IL-1β secretion.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-08-18
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/704011
https://dx.doi.org/10.1016/j.bbadis.2022.166525
url http://hdl.handle.net/10486/704011
https://dx.doi.org/10.1016/j.bbadis.2022.166525
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
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:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419275213602816
score 15,198674

Similares en LA Referencia