Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.
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Authors
Ricke-Hoch, MelanieStelling, Elisabeth
Lasswitz, Lisa
Gunesch, Antonia P
Kasten, Martina
Zapatero-Belinchón, Francisco J
Brogden, Graham
Gerold, Gisa
Pietschmann, Thomas
Montiel, Virginie
Balligand, Jean-Luc
Facciotti, Federica
Hirsch, Emilio
Gausepohl, Thomas
Elbahesh, Husni
Rimmelzwaan, Guus F
Höfer, Anne
Kühnel, Mark P
Jonigk, Danny
Eigendorf, Julian
Tegtbur, Uwe
Mink, Lena
Scherr, Michaela
Illig, Thomas
Schambach, Axel
Pfeffer, Tobias J
Hilfiker, Andres
Haverich, Axel
Hilfiker-Kleiner, Denise
Issue Date
2021-08-04
Metadata
Show full item recordAbstract
he SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglandin-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.Citation
PLoS One. 2021 Aug 4;16(8):e0255335. doi: 10.1371/journal.pone.0255335. PMID: 34347801.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
PLOSJournal
PloS onePubMed ID
34347801Type
ArticleLanguage
enEISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0255335
Scopus Count
The following license files are associated with this item:
- Creative Commons
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