Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis

Myocarditis is an inflammatory and oxidative disorder characterized by immune cell recruitment in the damaged tissue and organ dysfunction. In this paper, we evaluated the molecular pathways involved in myocarditis using a natural compound, <i>Coriolus versicolor</i>, in an experimental...

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Main Authors: Livia Interdonato, Daniela Impellizzeri, Ramona D’Amico, Marika Cordaro, Rosalba Siracusa, Melissa D’Agostino, Tiziana Genovese, Enrico Gugliandolo, Rosalia Crupi, Roberta Fusco, Salvatore Cuzzocrea, Rosanna Di Paola
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/12/8/1507
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author Livia Interdonato
Daniela Impellizzeri
Ramona D’Amico
Marika Cordaro
Rosalba Siracusa
Melissa D’Agostino
Tiziana Genovese
Enrico Gugliandolo
Rosalia Crupi
Roberta Fusco
Salvatore Cuzzocrea
Rosanna Di Paola
author_facet Livia Interdonato
Daniela Impellizzeri
Ramona D’Amico
Marika Cordaro
Rosalba Siracusa
Melissa D’Agostino
Tiziana Genovese
Enrico Gugliandolo
Rosalia Crupi
Roberta Fusco
Salvatore Cuzzocrea
Rosanna Di Paola
author_sort Livia Interdonato
collection DOAJ
description Myocarditis is an inflammatory and oxidative disorder characterized by immune cell recruitment in the damaged tissue and organ dysfunction. In this paper, we evaluated the molecular pathways involved in myocarditis using a natural compound, <i>Coriolus versicolor</i>, in an experimental model of autoimmune myocarditis (EAM). Animals were immunized with an emulsion of pig cardiac myosin and complete Freund’s adjuvant supplemented with mycobacterium tuberculosis; thereafter, <i>Coriolus versicolor</i> (200 mg/Kg) was orally administered for 21 days. At the end of the experiment, blood pressure and heart rate measurements were recorded and the body and heart weights as well. From the molecular point of view, the <i>Coriolus versicolor</i> administration reduced the activation of the TLR4/NF-κB pathway and the levels of pro-inflammatory cytokines (INF-γ, TNF-α, IL-6, IL-17, and IL-2) and restored the levels of anti-inflammatory cytokines (IL-10). These anti-inflammatory effects were accompanied with a reduced lipid peroxidation and nitrite levels and restored the antioxidant enzyme activities (SOD and CAT) and GSH levels. Additionally, it reduced the histological injury and the immune cell recruitment (CD4<sup>+</sup> and CD68<sup>+</sup> cells). Moreover, we observed an antiapoptotic activity in both intrinsic (Fas/FasL/caspase-3) and extrinsic (Bax/Bcl-2) pathways. Overall, our data showed that <i>Coriolus versicolor</i> administration modulates the TLR4/NF-κB signaling in EAM.
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spelling doaj.art-9f3b22ed08264607b459a531ecfa266c2023-11-19T00:00:52ZengMDPI AGAntioxidants2076-39212023-07-01128150710.3390/antiox12081507Modulation of TLR4/NFκB Pathways in Autoimmune MyocarditisLivia Interdonato0Daniela Impellizzeri1Ramona D’Amico2Marika Cordaro3Rosalba Siracusa4Melissa D’Agostino5Tiziana Genovese6Enrico Gugliandolo7Rosalia Crupi8Roberta Fusco9Salvatore Cuzzocrea10Rosanna Di Paola11Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Consolare Valeria, 98100 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Sciences, University of Messina, 98168 Messina, ItalyDepartment of Veterinary Sciences, University of Messina, 98168 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Sciences, University of Messina, 98168 Messina, ItalyMyocarditis is an inflammatory and oxidative disorder characterized by immune cell recruitment in the damaged tissue and organ dysfunction. In this paper, we evaluated the molecular pathways involved in myocarditis using a natural compound, <i>Coriolus versicolor</i>, in an experimental model of autoimmune myocarditis (EAM). Animals were immunized with an emulsion of pig cardiac myosin and complete Freund’s adjuvant supplemented with mycobacterium tuberculosis; thereafter, <i>Coriolus versicolor</i> (200 mg/Kg) was orally administered for 21 days. At the end of the experiment, blood pressure and heart rate measurements were recorded and the body and heart weights as well. From the molecular point of view, the <i>Coriolus versicolor</i> administration reduced the activation of the TLR4/NF-κB pathway and the levels of pro-inflammatory cytokines (INF-γ, TNF-α, IL-6, IL-17, and IL-2) and restored the levels of anti-inflammatory cytokines (IL-10). These anti-inflammatory effects were accompanied with a reduced lipid peroxidation and nitrite levels and restored the antioxidant enzyme activities (SOD and CAT) and GSH levels. Additionally, it reduced the histological injury and the immune cell recruitment (CD4<sup>+</sup> and CD68<sup>+</sup> cells). Moreover, we observed an antiapoptotic activity in both intrinsic (Fas/FasL/caspase-3) and extrinsic (Bax/Bcl-2) pathways. Overall, our data showed that <i>Coriolus versicolor</i> administration modulates the TLR4/NF-κB signaling in EAM.https://www.mdpi.com/2076-3921/12/8/1507experimental autoimmune myocarditisimmunomodulationoxidative stress
spellingShingle Livia Interdonato
Daniela Impellizzeri
Ramona D’Amico
Marika Cordaro
Rosalba Siracusa
Melissa D’Agostino
Tiziana Genovese
Enrico Gugliandolo
Rosalia Crupi
Roberta Fusco
Salvatore Cuzzocrea
Rosanna Di Paola
Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
Antioxidants
experimental autoimmune myocarditis
immunomodulation
oxidative stress
title Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
title_full Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
title_fullStr Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
title_full_unstemmed Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
title_short Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis
title_sort modulation of tlr4 nfκb pathways in autoimmune myocarditis
topic experimental autoimmune myocarditis
immunomodulation
oxidative stress
url https://www.mdpi.com/2076-3921/12/8/1507
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