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NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation

(1) Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to tar...

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Detalles Bibliográficos
Autores principales: Tesoro, Laura, Hernández, Ignacio, Ramírez-Carracedo, Rafael, Díez-Mata, Javier, Alcharani, Nunzio, Jiménez-Guirado, Beatriz, Ovejero-Paredes, Karina, Filice, Marco, Zamorano, Jose Luis, Saura, Marta, Zaragoza, Carlos, Botana, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608724/
https://www.ncbi.nlm.nih.gov/pubmed/36297479
http://dx.doi.org/10.3390/pharmaceutics14102044
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author Tesoro, Laura
Hernández, Ignacio
Ramírez-Carracedo, Rafael
Díez-Mata, Javier
Alcharani, Nunzio
Jiménez-Guirado, Beatriz
Ovejero-Paredes, Karina
Filice, Marco
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
Botana, Laura
author_facet Tesoro, Laura
Hernández, Ignacio
Ramírez-Carracedo, Rafael
Díez-Mata, Javier
Alcharani, Nunzio
Jiménez-Guirado, Beatriz
Ovejero-Paredes, Karina
Filice, Marco
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
Botana, Laura
author_sort Tesoro, Laura
collection PubMed
description (1) Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-ĸB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damage.
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spelling pubmed-96087242022-10-28 NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation Tesoro, Laura Hernández, Ignacio Ramírez-Carracedo, Rafael Díez-Mata, Javier Alcharani, Nunzio Jiménez-Guirado, Beatriz Ovejero-Paredes, Karina Filice, Marco Zamorano, Jose Luis Saura, Marta Zaragoza, Carlos Botana, Laura Pharmaceutics Article (1) Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-ĸB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damage. MDPI 2022-09-26 /pmc/articles/PMC9608724/ /pubmed/36297479 http://dx.doi.org/10.3390/pharmaceutics14102044 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tesoro, Laura
Hernández, Ignacio
Ramírez-Carracedo, Rafael
Díez-Mata, Javier
Alcharani, Nunzio
Jiménez-Guirado, Beatriz
Ovejero-Paredes, Karina
Filice, Marco
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
Botana, Laura
NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title_full NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title_fullStr NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title_full_unstemmed NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title_short NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-κB Activation
title_sort nil10: a new il10-receptor binding nanoparticle that induces cardiac protection in mice and pigs subjected to acute myocardial infarction through stat3/nf-κb activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608724/
https://www.ncbi.nlm.nih.gov/pubmed/36297479
http://dx.doi.org/10.3390/pharmaceutics14102044
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