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Tytuł:
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Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.
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Autorzy:
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Ricke-Hoch M; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.
Stelling E; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.
Lasswitz L; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.
Gunesch AP; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.; German Center for Infection Research, Hanover-Braunschweig Site, Braunschweig, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.
Kasten M; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.
Zapatero-Belinchón FJ; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.; Department of Clinical Microbiology, Virology & Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.
Brogden G; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.
Gerold G; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.; Department of Clinical Microbiology, Virology & Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.; Department of Biochemistry, University of Veterinary Medicine Hannover, Hanover Germany.
Pietschmann T; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hanover, Germany.; German Center for Infection Research, Hanover-Braunschweig Site, Braunschweig, Germany.
Montiel V; Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, and Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Balligand JL; Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, and Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Facciotti F; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.
Hirsch E; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
Gausepohl T; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.
Elbahesh H; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), Hannover, Germany.
Rimmelzwaan GF; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), Hannover, Germany.
Höfer A; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hanover, Germany.; Institute for Pathology, Hannover Medical School, Hanover, Germany.
Kühnel MP; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hanover, Germany.; Institute for Pathology, Hannover Medical School, Hanover, Germany.
Jonigk D; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hanover, Germany.; Institute for Pathology, Hannover Medical School, Hanover, Germany.
Eigendorf J; Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
Tegtbur U; Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
Mink L; Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
Scherr M; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hanover, Germany.
Illig T; Hannover Unified Biobank (HUB), Hannover Medical School, Hanover, Germany.
Schambach A; Institute of Experimental Hematology, Hannover Medical School, Hanover, Germany.; Division of Hematology and Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
Pfeffer TJ; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.
Hilfiker A; Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hanover, Germany.
Haverich A; Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hanover, Germany.
Hilfiker-Kleiner D; Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany.; Department of Cardiovascular Complications of Oncologic Therapies, Medical Faculty of the Philipps University Marburg, Marburg, Germany.
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Źródło:
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PloS one [PLoS One] 2021 Aug 04; Vol. 16 (8), pp. e0255335. Date of Electronic Publication: 2021 Aug 04 (Print Publication: 2021).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: San Francisco, CA : Public Library of Science
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MeSH Terms:
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Immunity*/drug effects
Immunity*/physiology
COVID-19/*pathology
Dinoprostone/*blood
Adolescent ; Adult ; Animals ; COVID-19/blood ; COVID-19/immunology ; Case-Control Studies ; Cells, Cultured ; Chlorocebus aethiops ; Dinoprostone/pharmacology ; Dinoprostone/physiology ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Vero Cells ; Young Adult
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Grant Information:
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International ERC_ European Research Council
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Substance Nomenclature:
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K7Q1JQR04M (Dinoprostone)
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Entry Date(s):
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Date Created: 20210804 Date Completed: 20210813 Latest Revision: 20231107
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Update Code:
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20240105
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PubMed Central ID:
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PMC8336874
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DOI:
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10.1371/journal.pone.0255335
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PMID:
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34347801
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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.
Competing Interests: The authors have declared that no competing interests exist.
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