SARS-CoV-2 Switches 'on' MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression

• Published in: Frontiers in pharmacology Vol. 12; p. 631879
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.04.2021
• Subjects: COVID-19; DUSP1; DUSP5; MAPK; NFkB; Pharmacology; SARS-CoV-2; COVID-19; DUSP5; SARS-CoV-2; DUSP1; chroloquine; NFkB; MAPK
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.631879

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 ( ). A comprehensive analysis of publicly available gene expression data sets of human airway epithelial cells (AECs) infected with SARS-CoV-2 identified and 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 . 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 and 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.