{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:39:35Z","timestamp":1788925175189,"version":"build-2803163510"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Mitogen-activated protein kinases (MAPK) and NF-kappaB (NF-\u03baB) pathway regulate many cellular processes and are essential for immune cells function. Their activity is controlled by dual-specificity phosphatases (<jats:italic>DUSPs<\/jats:italic>). A comprehensive analysis of publicly available gene expression data sets of human airway epithelial cells (AECs) infected with SARS-CoV-2 identified <jats:italic>DUSP1<\/jats:italic> and <jats:italic>DUSP5<\/jats:italic> among the lowest induced transcripts within these pathways. These proteins are known to downregulate MAPK and NF-\u03baB pathways; and their lower expression was associated with increased activity of MAPK and NF-\u03baB signaling and enhanced expression of proinflammatory cytokines such as <jats:italic>TNF-\u03b1<\/jats: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 <jats:italic>DUSP1<\/jats:italic> and <jats:italic>DUSP5<\/jats: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.<\/jats:p>","DOI":"10.3389\/fphar.2021.631879","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T06:09:00Z","timestamp":1618898940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":75,"title":["SARS-CoV-2 Switches \u2018on\u2019 MAPK and NF\u03baB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression"],"prefix":"10.3389","volume":"12","author":[{"given":"Swati","family":"Goel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Saheb Sharif-Askari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narjes","family":"Saheb Sharif Askari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Madkhana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Munzer","family":"Alwaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam","family":"Mahboub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel M","family":"Zakeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaref","family":"Ratemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat","family":"Hamoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qutayba","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabih","family":"Halwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1111\/cts.12862","article-title":"Effect of common medications on the expression of SARS-CoV-2 entry receptors in kidney tissue","volume":"13","author":"Alabed","year":"2020","journal-title":"Clin Transl Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1172\/JCI114265","article-title":"Neutrophil-activating peptide-1\/interleukin 8, a novel cytokine that activates neutrophils","volume":"84","author":"Baggiolini","year":"1989","journal-title":"J. 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