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.
【저자키워드】 COVID-19, SARS-CoV-2, MAPK, DUSP1, NFkB, DUSP5, chroloquine, 【초록키워드】 Treatment, Gene Expression, Chloroquine, immune, Protein, COVID-19 infection, pathway, expression, mechanism, TNF-α, NF-κB, Immune cell, regulate, Pathways, mitogen-activated protein kinase, data set, phosphatase, reduction, Proinflammatory cytokine, Activation, non-steroidal anti-inflammatory drug, comprehensive analysis, help, lower expression, regulatory pathway, NF-κB signaling, transcript, Genes, Cell, lowest, other coronavirus, human airway epithelial, cellular processe, downregulate, infected with SARS-CoV-2, the SARS-CoV-2, 【제목키워드】 NFκB,