Goel, S;
Saheb Sharif-Askari, F;
Saheb Sharif Askari, N;
Madkhana, B;
Alwaa, AM;
Mahboub, B;
Zakeri, AM;
... Halwani, R; + view all
(2021)
SARS-CoV-2 Switches 'on' MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression.
Frontiers in Pharmacology
, 12
, Article 631879. 10.3389/fphar.2021.631879.
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Abstract
Mitogen-activated protein kinases (MAPK) and NF-kappaB (NF-κB) pathway regulate many cellular processes and are essential for immune cells function. Their activity is controlled by dual-specificity phosphatases (DUSPs). A comprehensive analysis of publicly available gene expression data sets of human airway epithelial cells (AECs) infected with SARS-CoV-2 identified DUSP1 and DUSP5 among the lowest induced transcripts within these pathways. These proteins are known to downregulate MAPK and NF-κB pathways; and their lower expression was associated with increased activity of MAPK and NF-κB signaling and enhanced expression of proinflammatory cytokines such as TNF-α. Infection with other coronaviruses did not have a similar effect on these genes. Interestingly, treatment with chloroquine and/or non-steroidal anti-inflammatory drugs counteracted the SARS-CoV-2 induced reduction of DUSP1 and DUSP5 genes expression. Therapeutically, impeding this evasion mechanism of SARS-CoV-2 may help control the exaggerated activation of these immune regulatory pathways during a COVID-19 infection.
| Type: | Article |
|---|---|
| Title: | SARS-CoV-2 Switches 'on' MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fphar.2021.631879 |
| Publisher version: | https://doi.org/10.3389/fphar.2021.631879 |
| Language: | English |
| Additional information: | Copyright © 2021 Goel, Saheb Sharif-Askari, Saheb Sharif Askari, Madkhana, Alwaa, Mahboub, Zakeri, Ratemi, Hamoudi, Hamid and Halwani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | SARS-CoV-2, COVID-19, MAPK, NFkB, DUSP1, DUSP5, chroloquine |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148992 |
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