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CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5...

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Autores principales: Ferrero, Maximiliano Ruben, Garcia, Cristiana Couto, Dutra de Almeida, Marcella, Torres Braz da Silva, Jullian, Bianchi Reis Insuela, Daniella, Teixeira Ferreira, Tatiana Paula, de Sá Coutinho, Diego, Trindade de Azevedo, Carolina, Machado Rodrigues e Silva, Patrícia, Martins, Marco Aurélio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308708/
https://www.ncbi.nlm.nih.gov/pubmed/34203121
http://dx.doi.org/10.3390/ph14070620
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author Ferrero, Maximiliano Ruben
Garcia, Cristiana Couto
Dutra de Almeida, Marcella
Torres Braz da Silva, Jullian
Bianchi Reis Insuela, Daniella
Teixeira Ferreira, Tatiana Paula
de Sá Coutinho, Diego
Trindade de Azevedo, Carolina
Machado Rodrigues e Silva, Patrícia
Martins, Marco Aurélio
author_facet Ferrero, Maximiliano Ruben
Garcia, Cristiana Couto
Dutra de Almeida, Marcella
Torres Braz da Silva, Jullian
Bianchi Reis Insuela, Daniella
Teixeira Ferreira, Tatiana Paula
de Sá Coutinho, Diego
Trindade de Azevedo, Carolina
Machado Rodrigues e Silva, Patrícia
Martins, Marco Aurélio
author_sort Ferrero, Maximiliano Ruben
collection PubMed
description Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.
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spelling pubmed-83087082021-07-25 CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice Ferrero, Maximiliano Ruben Garcia, Cristiana Couto Dutra de Almeida, Marcella Torres Braz da Silva, Jullian Bianchi Reis Insuela, Daniella Teixeira Ferreira, Tatiana Paula de Sá Coutinho, Diego Trindade de Azevedo, Carolina Machado Rodrigues e Silva, Patrícia Martins, Marco Aurélio Pharmaceuticals (Basel) Article Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD. MDPI 2021-06-28 /pmc/articles/PMC8308708/ /pubmed/34203121 http://dx.doi.org/10.3390/ph14070620 Text en © 2021 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
Ferrero, Maximiliano Ruben
Garcia, Cristiana Couto
Dutra de Almeida, Marcella
Torres Braz da Silva, Jullian
Bianchi Reis Insuela, Daniella
Teixeira Ferreira, Tatiana Paula
de Sá Coutinho, Diego
Trindade de Azevedo, Carolina
Machado Rodrigues e Silva, Patrícia
Martins, Marco Aurélio
CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title_full CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title_fullStr CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title_full_unstemmed CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title_short CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
title_sort ccr5 antagonist maraviroc inhibits acute exacerbation of lung inflammation triggered by influenza virus in cigarette smoke-exposed mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308708/
https://www.ncbi.nlm.nih.gov/pubmed/34203121
http://dx.doi.org/10.3390/ph14070620
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