tetano
Editor, Senior Moderator
PLoS One
. 2021 Aug 4;16(8):e0255335.
doi: 10.1371/journal.pone.0255335. eCollection 2021.
Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
Melanie Ricke-Hoch[SUP] 1 [/SUP], Elisabeth Stelling[SUP] 1 [/SUP], Lisa Lasswitz[SUP] 2 [/SUP], Antonia P Gunesch[SUP] 2 3 4 [/SUP], Martina Kasten[SUP] 1 [/SUP], Francisco J Zapatero-Belinchón[SUP] 2 5 [/SUP], Graham Brogden[SUP] 2 [/SUP], Gisa Gerold[SUP] 2 5 6 [/SUP], Thomas Pietschmann[SUP] 2 3 [/SUP], Virginie Montiel[SUP] 7 [/SUP], Jean-Luc Balligand[SUP] 7 [/SUP], Federica Facciotti[SUP] 8 [/SUP], Emilio Hirsch[SUP] 9 [/SUP], Thomas Gausepohl[SUP] 1 [/SUP], Husni Elbahesh[SUP] 10 [/SUP], Guus F Rimmelzwaan[SUP] 10 [/SUP], Anne Höfer[SUP] 11 12 [/SUP], Mark P Kühnel[SUP] 11 12 [/SUP], Danny Jonigk[SUP] 11 12 [/SUP], Julian Eigendorf[SUP] 13 [/SUP], Uwe Tegtbur[SUP] 13 [/SUP], Lena Mink[SUP] 13 [/SUP], Michaela Scherr[SUP] 14 [/SUP], Thomas Illig[SUP] 15 [/SUP], Axel Schambach[SUP] 16 17 [/SUP], Tobias J Pfeffer[SUP] 1 [/SUP], Andres Hilfiker[SUP] 18 [/SUP], Axel Haverich[SUP] 18 [/SUP], Denise Hilfiker-Kleiner[SUP] 1 19 [/SUP]
Affiliations
Abstract
The 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.
. 2021 Aug 4;16(8):e0255335.
doi: 10.1371/journal.pone.0255335. eCollection 2021.
Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
Melanie Ricke-Hoch[SUP] 1 [/SUP], Elisabeth Stelling[SUP] 1 [/SUP], Lisa Lasswitz[SUP] 2 [/SUP], Antonia P Gunesch[SUP] 2 3 4 [/SUP], Martina Kasten[SUP] 1 [/SUP], Francisco J Zapatero-Belinchón[SUP] 2 5 [/SUP], Graham Brogden[SUP] 2 [/SUP], Gisa Gerold[SUP] 2 5 6 [/SUP], Thomas Pietschmann[SUP] 2 3 [/SUP], Virginie Montiel[SUP] 7 [/SUP], Jean-Luc Balligand[SUP] 7 [/SUP], Federica Facciotti[SUP] 8 [/SUP], Emilio Hirsch[SUP] 9 [/SUP], Thomas Gausepohl[SUP] 1 [/SUP], Husni Elbahesh[SUP] 10 [/SUP], Guus F Rimmelzwaan[SUP] 10 [/SUP], Anne Höfer[SUP] 11 12 [/SUP], Mark P Kühnel[SUP] 11 12 [/SUP], Danny Jonigk[SUP] 11 12 [/SUP], Julian Eigendorf[SUP] 13 [/SUP], Uwe Tegtbur[SUP] 13 [/SUP], Lena Mink[SUP] 13 [/SUP], Michaela Scherr[SUP] 14 [/SUP], Thomas Illig[SUP] 15 [/SUP], Axel Schambach[SUP] 16 17 [/SUP], Tobias J Pfeffer[SUP] 1 [/SUP], Andres Hilfiker[SUP] 18 [/SUP], Axel Haverich[SUP] 18 [/SUP], Denise Hilfiker-Kleiner[SUP] 1 19 [/SUP]
Affiliations
- PMID: 34347801
- DOI: 10.1371/journal.pone.0255335
Abstract
The 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.