SARS-CoV-2 Switches 'on' MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression.
Front Pharmacol
; 12: 631879, 2021.
Article
in English
| MEDLINE | ID: covidwho-1488443
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
Language:
English
Journal:
Front Pharmacol
Year:
2021
Document Type:
Article
Affiliation country:
Fphar.2021.631879
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