AUTHOR=Goel Swati , Saheb Sharif-Askari Fatemeh , Saheb Sharif Askari Narjes , Madkhana Bushra , Alwaa Ahmad Munzer , Mahboub Bassam , Zakeri Adel M , Ratemi Elaref , Hamoudi Rifat , Hamid Qutayba , Halwani Rabih 

TITLE=SARS-CoV-2 Switches ‘on’ MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.631879

DOI=10.3389/fphar.2021.631879

ISSN=1663-9812

ABSTRACT=<p>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 (<italic>DUSPs</italic>). A comprehensive analysis of publicly available gene expression data sets of human airway epithelial cells (AECs) infected with SARS-CoV-2 identified <italic>DUSP1</italic> and <italic>DUSP5</italic> 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 <italic>TNF-α</italic>. 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 <italic>DUSP1</italic> and <italic>DUSP5</italic> 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.</p>