The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages

Autores
Muñoz, Marcos David; Della Vedova, Maria Cecilia; Gomez-Mejiba, Sandra Esther; Ramirez, Dario
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. M1-like macrophages produce reactive oxygen species, inflammatory cytokines (IL-1b, IFNb), express inflammatory protein such as nitric oxide synthase (iNOS) and surface markers such as CD80; CD86; CD14; CD44. Because M1-like activation contributes to inflammation, decoding its mechanism may lead to find novel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing its chain reactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its free radical trapping properties. Herein, we hypothesize that DMPO can reduce LPS-induced M1-like activation of macrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cells with 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 6h or 24h. Cells were used for the mRNA detection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing the inflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferon signaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique for IFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1 expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggered M1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.
Fil: Muñoz, Marcos David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Della Vedova, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
DMPO
INFLAMMATION
LIPOPOLYSACCHARIDE
MACROPHAGE
TRANSCRIPTOMICS
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:11336/89283
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed MacrophagesMuñoz, Marcos DavidDella Vedova, Maria CeciliaGomez-Mejiba, Sandra EstherRamirez, DarioDMPOINFLAMMATIONLIPOPOLYSACCHARIDEMACROPHAGETRANSCRIPTOMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. M1-like macrophages produce reactive oxygen species, inflammatory cytokines (IL-1b, IFNb), express inflammatory protein such as nitric oxide synthase (iNOS) and surface markers such as CD80; CD86; CD14; CD44. Because M1-like activation contributes to inflammation, decoding its mechanism may lead to find novel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing its chain reactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its free radical trapping properties. Herein, we hypothesize that DMPO can reduce LPS-induced M1-like activation of macrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cells with 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 6h or 24h. Cells were used for the mRNA detection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing the inflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferon signaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique for IFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1 expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggered M1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.Fil: Muñoz, Marcos David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Della Vedova, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaPharmaceutical and Chemical Journal2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89283Muñoz, Marcos David; Della Vedova, Maria Cecilia; Gomez-Mejiba, Sandra Esther; Ramirez, Dario; The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages; Pharmaceutical and Chemical Journal; Pharmaceutical and Chemical Journal; 5; 2; 6-2018; 1-82349-7092CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://tpcj.org/download/vol-5-iss-2-2018/TPCJ2018-05-02-01-08.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:38:58Zoai:ri.conicet.gov.ar:11336/89283instacron: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:34982025-09-29 10:38:59.264CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
title The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
spellingShingle The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
Muñoz, Marcos David
DMPO
INFLAMMATION
LIPOPOLYSACCHARIDE
MACROPHAGE
TRANSCRIPTOMICS
title_short The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
title_full The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
title_fullStr The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
title_full_unstemmed The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
title_sort The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
dc.creator.none.fl_str_mv Muñoz, Marcos David
Della Vedova, Maria Cecilia
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author Muñoz, Marcos David
author_facet Muñoz, Marcos David
Della Vedova, Maria Cecilia
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author_role author
author2 Della Vedova, Maria Cecilia
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author2_role author
author
author
dc.subject.none.fl_str_mv DMPO
INFLAMMATION
LIPOPOLYSACCHARIDE
MACROPHAGE
TRANSCRIPTOMICS
topic DMPO
INFLAMMATION
LIPOPOLYSACCHARIDE
MACROPHAGE
TRANSCRIPTOMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. M1-like macrophages produce reactive oxygen species, inflammatory cytokines (IL-1b, IFNb), express inflammatory protein such as nitric oxide synthase (iNOS) and surface markers such as CD80; CD86; CD14; CD44. Because M1-like activation contributes to inflammation, decoding its mechanism may lead to find novel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing its chain reactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its free radical trapping properties. Herein, we hypothesize that DMPO can reduce LPS-induced M1-like activation of macrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cells with 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 6h or 24h. Cells were used for the mRNA detection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing the inflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferon signaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique for IFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1 expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggered M1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.
Fil: Muñoz, Marcos David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Della Vedova, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. M1-like macrophages produce reactive oxygen species, inflammatory cytokines (IL-1b, IFNb), express inflammatory protein such as nitric oxide synthase (iNOS) and surface markers such as CD80; CD86; CD14; CD44. Because M1-like activation contributes to inflammation, decoding its mechanism may lead to find novel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing its chain reactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its free radical trapping properties. Herein, we hypothesize that DMPO can reduce LPS-induced M1-like activation of macrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cells with 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 6h or 24h. Cells were used for the mRNA detection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing the inflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferon signaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique for IFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1 expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggered M1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.
publishDate 2018
dc.date.none.fl_str_mv 2018-06
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/11336/89283
Muñoz, Marcos David; Della Vedova, Maria Cecilia; Gomez-Mejiba, Sandra Esther; Ramirez, Dario; The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages; Pharmaceutical and Chemical Journal; Pharmaceutical and Chemical Journal; 5; 2; 6-2018; 1-8
2349-7092
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89283
identifier_str_mv Muñoz, Marcos David; Della Vedova, Maria Cecilia; Gomez-Mejiba, Sandra Esther; Ramirez, Dario; The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages; Pharmaceutical and Chemical Journal; Pharmaceutical and Chemical Journal; 5; 2; 6-2018; 1-8
2349-7092
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://tpcj.org/download/vol-5-iss-2-2018/TPCJ2018-05-02-01-08.pdf
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pharmaceutical and Chemical Journal
publisher.none.fl_str_mv Pharmaceutical and Chemical Journal
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 13.070432

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