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Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice

An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the pot...

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Autores principales: Tahamtan, Alireza, Samieipoor, Yazdan, Nayeri, Fatemeh Sadat, Rahbarimanesh, Ali Akbar, Izadi, Anahita, Rashidi-Nezhad, Ali, Tavakoli-Yaraki, Masoumeh, Farahmand, Mohammad, Bont, Louis, Shokri, Fazel, Mokhatri-Azad, Talat, Salimi, Vahid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955186/
https://www.ncbi.nlm.nih.gov/pubmed/28992427
http://dx.doi.org/10.1080/21505594.2017.1389369
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author Tahamtan, Alireza
Samieipoor, Yazdan
Nayeri, Fatemeh Sadat
Rahbarimanesh, Ali Akbar
Izadi, Anahita
Rashidi-Nezhad, Ali
Tavakoli-Yaraki, Masoumeh
Farahmand, Mohammad
Bont, Louis
Shokri, Fazel
Mokhatri-Azad, Talat
Salimi, Vahid
author_facet Tahamtan, Alireza
Samieipoor, Yazdan
Nayeri, Fatemeh Sadat
Rahbarimanesh, Ali Akbar
Izadi, Anahita
Rashidi-Nezhad, Ali
Tavakoli-Yaraki, Masoumeh
Farahmand, Mohammad
Bont, Louis
Shokri, Fazel
Mokhatri-Azad, Talat
Salimi, Vahid
author_sort Tahamtan, Alireza
collection PubMed
description An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221–8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092–4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology.
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spelling pubmed-59551862018-05-21 Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice Tahamtan, Alireza Samieipoor, Yazdan Nayeri, Fatemeh Sadat Rahbarimanesh, Ali Akbar Izadi, Anahita Rashidi-Nezhad, Ali Tavakoli-Yaraki, Masoumeh Farahmand, Mohammad Bont, Louis Shokri, Fazel Mokhatri-Azad, Talat Salimi, Vahid Virulence Research Paper An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221–8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092–4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology. Taylor & Francis 2017-12-08 /pmc/articles/PMC5955186/ /pubmed/28992427 http://dx.doi.org/10.1080/21505594.2017.1389369 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Tahamtan, Alireza
Samieipoor, Yazdan
Nayeri, Fatemeh Sadat
Rahbarimanesh, Ali Akbar
Izadi, Anahita
Rashidi-Nezhad, Ali
Tavakoli-Yaraki, Masoumeh
Farahmand, Mohammad
Bont, Louis
Shokri, Fazel
Mokhatri-Azad, Talat
Salimi, Vahid
Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title_full Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title_fullStr Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title_full_unstemmed Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title_short Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
title_sort effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955186/
https://www.ncbi.nlm.nih.gov/pubmed/28992427
http://dx.doi.org/10.1080/21505594.2017.1389369
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