In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation

Villacorta, Luis - Minarrieta, Lucia - Salvatore, Sonia R. - Khoo, Nicholas K. - Rom, Oren - Gao, Zhen - Berman, Rebecca C. - Jobbagy, Soma - Li, Lihua - Woodcock, Steven R. - Chen, Y. Eugene - Freeman, Bruce A. - Ferreira, Ana M. - Schopfer, Francisco J. - Vitturi, Dario A.

Resumen:

Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitroconjugated linoleic acid (NO2-CLA). Herein, NO2-CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO2-CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO2-CLA were recapitulated in a mouse peritonitis model where NO2-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO2-CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes.

Detalles Bibliográficos
2018
Agencia Nacional de Investigación e Innovación (ANII)
Comisión Sectorial de Investigación Científica (CSIC)
Nitro-fatty acid
Electrophile
Inflammation
Macrophage
Nrf2
NF-κB
Nitration
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/50838
Acceso abierto
Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
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author Villacorta, Luis
author2 Minarrieta, Lucia
Salvatore, Sonia R.
Khoo, Nicholas K.
Rom, Oren
Gao, Zhen
Berman, Rebecca C.
Jobbagy, Soma
Li, Lihua
Woodcock, Steven R.
Chen, Y. Eugene
Freeman, Bruce A.
Ferreira, Ana M.
Schopfer, Francisco J.
Vitturi, Dario A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Villacorta, Luis
Minarrieta, Lucia
Salvatore, Sonia R.
Khoo, Nicholas K.
Rom, Oren
Gao, Zhen
Berman, Rebecca C.
Jobbagy, Soma
Li, Lihua
Woodcock, Steven R.
Chen, Y. Eugene
Freeman, Bruce A.
Ferreira, Ana M.
Schopfer, Francisco J.
Vitturi, Dario A.
author_role author
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collection COLIBRI
dc.contributor.filiacion.none.fl_str_mv Villacorta Luis, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal Medicine
Minarrieta Lucia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Salvatore Sonia R., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Khoo Nicholas K., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Rom Oren, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal Medicine
Gao Zhen, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal Medicine
Berman Rebecca C., University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal Medicine
Jobbagy Soma, University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Li Lihua, University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Woodcock Steven R., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Chen Y. Eugene, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Cardiac Surgery
Freeman Bruce A., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Ferreira Ana M., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Schopfer Francisco J., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
Vitturi Dario A., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology
dc.creator.none.fl_str_mv Villacorta, Luis
Minarrieta, Lucia
Salvatore, Sonia R.
Khoo, Nicholas K.
Rom, Oren
Gao, Zhen
Berman, Rebecca C.
Jobbagy, Soma
Li, Lihua
Woodcock, Steven R.
Chen, Y. Eugene
Freeman, Bruce A.
Ferreira, Ana M.
Schopfer, Francisco J.
Vitturi, Dario A.
dc.date.accessioned.none.fl_str_mv 2025-07-31T16:14:01Z
dc.date.available.none.fl_str_mv 2025-07-31T16:14:01Z
dc.date.issued.none.fl_str_mv 2018
dc.description.abstract.none.fl_txt_mv Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitroconjugated linoleic acid (NO2-CLA). Herein, NO2-CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO2-CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO2-CLA were recapitulated in a mouse peritonitis model where NO2-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO2-CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes.
dc.description.sponsorship.none.fl_txt_mv Agencia Nacional de Investigación e Innovación (ANII)
Comisión Sectorial de Investigación Científica (CSIC)
dc.format.mimetype.es.fl_str_mv application/pdf
dc.identifier.citation.es.fl_str_mv VILLACORTA, L., MINARRIETA, L., SALVATORE, SR., y otros. In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biol [en línea] 2018, 15. DOI: 10.1016/j.redox.2018.01.005
dc.identifier.doi.none.fl_str_mv 10.1016/j.redox.2018.01.005
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/50838
dc.language.iso.none.fl_str_mv en
eng
dc.relation.none.fl_str_mv Redox Biol. 15, 2018
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.fl_str_mv Nitro-fatty acid
Electrophile
Inflammation
Macrophage
Nrf2
NF-κB
Nitration
dc.title.none.fl_str_mv In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitroconjugated linoleic acid (NO2-CLA). Herein, NO2-CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO2-CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO2-CLA were recapitulated in a mouse peritonitis model where NO2-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO2-CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes.
eu_rights_str_mv openAccess
format article
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identifier_str_mv VILLACORTA, L., MINARRIETA, L., SALVATORE, SR., y otros. In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biol [en línea] 2018, 15. DOI: 10.1016/j.redox.2018.01.005
10.1016/j.redox.2018.01.005
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institution Universidad de la República
instname_str Universidad de la República
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publishDate 2018
reponame_str COLIBRI
repository.mail.fl_str_mv karina.camps@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
repository_id_str 4771
rights_invalid_str_mv Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
spelling Villacorta Luis, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal MedicineMinarrieta Lucia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaSalvatore Sonia R., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyKhoo Nicholas K., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyRom Oren, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal MedicineGao Zhen, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal MedicineBerman Rebecca C., University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Internal MedicineJobbagy Soma, University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyLi Lihua, University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyWoodcock Steven R., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyChen Y. Eugene, University of Michigan Medical Center (Estados Unidos). Frankel Cardiovascular Center. Department of Cardiac SurgeryFreeman Bruce A., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyFerreira Ana M., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaSchopfer Francisco J., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical BiologyVitturi Dario A., University of Pittsburgh (Estados Unidos). Department of Pharmacology and Chemical Biology2025-07-31T16:14:01Z2025-07-31T16:14:01Z2018VILLACORTA, L., MINARRIETA, L., SALVATORE, SR., y otros. In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biol [en línea] 2018, 15. DOI: 10.1016/j.redox.2018.01.005https://hdl.handle.net/20.500.12008/5083810.1016/j.redox.2018.01.005Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitroconjugated linoleic acid (NO2-CLA). Herein, NO2-CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO2-CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO2-CLA were recapitulated in a mouse peritonitis model where NO2-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO2-CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes.Submitted by Haller Mariana (mhaller@higiene.edu.uy) on 2025-07-31T15:03:09Z No. of bitstreams: 2 license_rdf: 26539 bytes, checksum: 3b50ae24bd8bd076d49a70878a8a2d2c (MD5) In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation.pdf: 1615829 bytes, checksum: c448b074b1bcfe0444304fd6073f80e7 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2025-07-31T16:14:01Z (GMT). No. of bitstreams: 2 license_rdf: 26539 bytes, checksum: 3b50ae24bd8bd076d49a70878a8a2d2c (MD5) In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation.pdf: 1615829 bytes, checksum: c448b074b1bcfe0444304fd6073f80e7 (MD5) Previous issue date: 2018Agencia Nacional de Investigación e Innovación (ANII)Comisión Sectorial de Investigación Científica (CSIC)application/pdfenengRedox Biol. 15, 2018Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. 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- Universidad de la Repúblicafalse
spellingShingle In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
Villacorta, Luis
Nitro-fatty acid
Electrophile
Inflammation
Macrophage
Nrf2
NF-κB
Nitration
status_str publishedVersion
title In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
title_full In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
title_fullStr In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
title_full_unstemmed In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
title_short In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
title_sort In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation
topic Nitro-fatty acid
Electrophile
Inflammation
Macrophage
Nrf2
NF-κB
Nitration
url https://hdl.handle.net/20.500.12008/50838