SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 e...

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Autores principales: Saheb Sharif-Askari, Fatemeh, Saheb Sharif-Askari, Narjes, Goel, Swati, Hafezi, Shirin, Assiri, Rasha, Al-Muhsen, Saleh, Hamid, Qutayba, Halwani, Rabih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295491/
https://www.ncbi.nlm.nih.gov/pubmed/34303662
http://dx.doi.org/10.1016/j.ejphar.2021.174374
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author Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Goel, Swati
Hafezi, Shirin
Assiri, Rasha
Al-Muhsen, Saleh
Hamid, Qutayba
Halwani, Rabih
author_facet Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Goel, Swati
Hafezi, Shirin
Assiri, Rasha
Al-Muhsen, Saleh
Hamid, Qutayba
Halwani, Rabih
author_sort Saheb Sharif-Askari, Fatemeh
collection PubMed
description The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.
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spelling pubmed-82954912021-07-22 SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway Saheb Sharif-Askari, Fatemeh Saheb Sharif-Askari, Narjes Goel, Swati Hafezi, Shirin Assiri, Rasha Al-Muhsen, Saleh Hamid, Qutayba Halwani, Rabih Eur J Pharmacol Article The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect. Elsevier B.V. 2021-10-05 2021-07-22 /pmc/articles/PMC8295491/ /pubmed/34303662 http://dx.doi.org/10.1016/j.ejphar.2021.174374 Text en © 2021 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Goel, Swati
Hafezi, Shirin
Assiri, Rasha
Al-Muhsen, Saleh
Hamid, Qutayba
Halwani, Rabih
SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title_full SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title_fullStr SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title_full_unstemmed SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title_short SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
title_sort sars-cov-2 attenuates corticosteroid sensitivity by suppressing dusp1 expression and activating p38 mapk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295491/
https://www.ncbi.nlm.nih.gov/pubmed/34303662
http://dx.doi.org/10.1016/j.ejphar.2021.174374
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