BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism
BRCA-1 is a nuclear protein involved in DNA repair, transcriptional regulation, and cell cycle control. Its involvement in other cellular processes has been described. Here, we aimed to investigate the role of BRCA-1 in macrophages M(LPS), M(IL-4), and tumor cell-induced differentiation. We used siR...
- Autores:
-
da Silva Morrone, Maurilio
Somensi, Nauana
Franz, Lucas
de Miranda Ramos, Vitor
Gasparotto, Juciano
Taís da Rosa, Helen
Sartori, Marcelo
Figueiró, Fabrício
Gelain, Daniel
ZANOTTO-FILHO, ALFEU
Moreira, José Cláudio Fonseca
- Tipo de recurso:
- http://purl.org/coar/resource_type/c_816b
- Fecha de publicación:
- 2019
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/5657
- Acceso en línea:
- https://hdl.handle.net/11323/5657
https://repositorio.cuc.edu.co/
- Palabra clave:
- BRCA-1
Inflammation
M(LPS) and M(IL-4) polarization
Macrophage activation
- Rights
- openAccess
- License
- CC0 1.0 Universal
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RCUC2_08a3686156369be44859d416e044bfd8 |
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oai:repositorio.cuc.edu.co:11323/5657 |
network_acronym_str |
RCUC2 |
network_name_str |
REDICUC - Repositorio CUC |
repository_id_str |
|
dc.title.spa.fl_str_mv |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
title |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
spellingShingle |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism BRCA-1 Inflammation M(LPS) and M(IL-4) polarization Macrophage activation |
title_short |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
title_full |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
title_fullStr |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
title_full_unstemmed |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
title_sort |
BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism |
dc.creator.fl_str_mv |
da Silva Morrone, Maurilio Somensi, Nauana Franz, Lucas de Miranda Ramos, Vitor Gasparotto, Juciano Taís da Rosa, Helen Sartori, Marcelo Figueiró, Fabrício Gelain, Daniel ZANOTTO-FILHO, ALFEU Moreira, José Cláudio Fonseca |
dc.contributor.author.spa.fl_str_mv |
da Silva Morrone, Maurilio Somensi, Nauana Franz, Lucas de Miranda Ramos, Vitor Gasparotto, Juciano Taís da Rosa, Helen Sartori, Marcelo Figueiró, Fabrício Gelain, Daniel ZANOTTO-FILHO, ALFEU Moreira, José Cláudio Fonseca |
dc.subject.spa.fl_str_mv |
BRCA-1 Inflammation M(LPS) and M(IL-4) polarization Macrophage activation |
topic |
BRCA-1 Inflammation M(LPS) and M(IL-4) polarization Macrophage activation |
description |
BRCA-1 is a nuclear protein involved in DNA repair, transcriptional regulation, and cell cycle control. Its involvement in other cellular processes has been described. Here, we aimed to investigate the role of BRCA-1 in macrophages M(LPS), M(IL-4), and tumor cell-induced differentiation. We used siRNAs to knockdown BRCA-1 in RAW 264.7 macrophages exposed to LPS, IL-4, and C6 glioma cells conditioned medium (CMC6), and evaluated macrophage differentiation markers and functional phagocytic activity as well as DNA damage and cell survival in the presence and absence of BRCA-1. LPS and CMC6, but not by IL-4, increased DNA damage in macrophages, and this effect was more pronounced in BRCA-1-depleted cells, including M(IL-4). BRCA-1 depletion impaired expression of pro-inflammatory cytokines, TNF-α and IL-6, and reduced the phagocytic activity of macrophages in response to LPS. In CMC6-induced differentiation, BRCA-1 knockdown inhibited TNF-α and IL-6 expression which was accompanied by upregulation of the anti-inflammatory markers IL-10 and TGF-β and reduced phagocytosis. In contrast, M(IL-4) phenotype was not affected by BRCA-1 status. Molecular docking predicted that the conserved BRCA-1 domain BRCT can interact with the p65 subunit of NF-κB. Immunofluorescence assays showed that BRCA-1 and p65 co-localize in the nucleus of LPS-treated macrophages and reporter gene assay showed that depletion of BRCA-1 decreased LPS and CMC6-induced NF-κB transactivation. IL-4 had no effect upon NF-κB. Taken together, our findings suggest a role of BRCA-1 in macrophage differentiation and phagocytosis induced by LPS and tumor cells secretoma, but not IL-4, in a mechanism associated with inhibition of NF-κB. |
publishDate |
2019 |
dc.date.accessioned.none.fl_str_mv |
2019-11-14T20:24:41Z |
dc.date.available.none.fl_str_mv |
2019-11-14T20:24:41Z |
dc.date.issued.none.fl_str_mv |
2019-12 |
dc.type.spa.fl_str_mv |
Pre-Publicación |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_816b |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/preprint |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ARTOTR |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
format |
http://purl.org/coar/resource_type/c_816b |
status_str |
acceptedVersion |
dc.identifier.uri.spa.fl_str_mv |
https://hdl.handle.net/11323/5657 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
url |
https://hdl.handle.net/11323/5657 https://repositorio.cuc.edu.co/ |
identifier_str_mv |
Corporación Universidad de la Costa REDICUC - Repositorio CUC |
dc.language.iso.none.fl_str_mv |
eng |
language |
eng |
dc.rights.spa.fl_str_mv |
CC0 1.0 Universal |
dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/publicdomain/zero/1.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
rights_invalid_str_mv |
CC0 1.0 Universal http://creativecommons.org/publicdomain/zero/1.0/ http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.publisher.spa.fl_str_mv |
Universidad de la Costa |
institution |
Corporación Universidad de la Costa |
bitstream.url.fl_str_mv |
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spelling |
da Silva Morrone, MaurilioSomensi, NauanaFranz, Lucasde Miranda Ramos, VitorGasparotto, JucianoTaís da Rosa, HelenSartori, MarceloFigueiró, FabrícioGelain, DanielZANOTTO-FILHO, ALFEUMoreira, José Cláudio Fonseca2019-11-14T20:24:41Z2019-11-14T20:24:41Z2019-12https://hdl.handle.net/11323/5657Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/BRCA-1 is a nuclear protein involved in DNA repair, transcriptional regulation, and cell cycle control. Its involvement in other cellular processes has been described. Here, we aimed to investigate the role of BRCA-1 in macrophages M(LPS), M(IL-4), and tumor cell-induced differentiation. We used siRNAs to knockdown BRCA-1 in RAW 264.7 macrophages exposed to LPS, IL-4, and C6 glioma cells conditioned medium (CMC6), and evaluated macrophage differentiation markers and functional phagocytic activity as well as DNA damage and cell survival in the presence and absence of BRCA-1. LPS and CMC6, but not by IL-4, increased DNA damage in macrophages, and this effect was more pronounced in BRCA-1-depleted cells, including M(IL-4). BRCA-1 depletion impaired expression of pro-inflammatory cytokines, TNF-α and IL-6, and reduced the phagocytic activity of macrophages in response to LPS. In CMC6-induced differentiation, BRCA-1 knockdown inhibited TNF-α and IL-6 expression which was accompanied by upregulation of the anti-inflammatory markers IL-10 and TGF-β and reduced phagocytosis. In contrast, M(IL-4) phenotype was not affected by BRCA-1 status. Molecular docking predicted that the conserved BRCA-1 domain BRCT can interact with the p65 subunit of NF-κB. Immunofluorescence assays showed that BRCA-1 and p65 co-localize in the nucleus of LPS-treated macrophages and reporter gene assay showed that depletion of BRCA-1 decreased LPS and CMC6-induced NF-κB transactivation. IL-4 had no effect upon NF-κB. Taken together, our findings suggest a role of BRCA-1 in macrophage differentiation and phagocytosis induced by LPS and tumor cells secretoma, but not IL-4, in a mechanism associated with inhibition of NF-κB.da Silva Morrone, Maurilio-will be generated-orcid-0000-0001-8144-0347-600Somensi, Nauana-will be generated-orcid-0000-0003-0440-7249-600Franz, Lucasde Miranda Ramos, Vitor-will be generated-orcid-0000-0001-7004-0823-600Gasparotto, Juciano-will be generated-orcid-0000-0003-2545-7288-600Taís da Rosa, HelenSartori, Marcelo-will be generated-orcid-0000-0003-4999-3122-600Figueiró, Fabrício-will be generated-orcid-0000-0003-0899-6407-600Gelain, Daniel-will be generated-orcid-0000-0001-5254-0509-600ZANOTTO-FILHO, ALFEU-will be generated-orcid-0000-0002-4188-3095-600Moreira, José Cláudio Fonseca-will be generated-orcid-0000-0002-0619-4913-600engUniversidad de la CostaCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2BRCA-1InflammationM(LPS) and M(IL-4) polarizationMacrophage activationBRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanismPre-Publicaciónhttp://purl.org/coar/resource_type/c_816bTextinfo:eu-repo/semantics/preprinthttp://purl.org/redcol/resource_type/ARTOTRinfo:eu-repo/semantics/acceptedVersionPublicationORIGINALBRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism.pdfBRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism.pdfapplication/pdf84775https://repositorio.cuc.edu.co/bitstreams/31297a7f-996a-40f1-88c3-f3536ef5e886/download56b592e650a427016d0d878709adfff7MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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