scholarly journals SARS-CoV-2-induced impaired immune response by Prostaglandin E2 is accelerated by age, male sex and air pollution

2020 ◽  
Author(s):  
Melanie Ricke-Hoch ◽  
Elisabeth Stelling ◽  
Lisa Lasswitz ◽  
Antonia-Patricia Gunesch ◽  
Martina Kasten ◽  
...  
Keyword(s):  
Air Pollution ◽  
B Cells ◽  
Prostaglandin E2 ◽  
Severe Disease ◽  
Lung Epithelial Cells ◽  
Pge2 Production ◽  
Blood Levels ◽  
B Cell Survival ◽  
Male Sex ◽  
Cox 2

Abstract The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds prostaglandin E2 (PGE2) blood levels elevated in COVID-19 patients with positive correlation 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-lung-precision-slices infected with SARS-CoV-2 display upregulated COX-2. PGE2 in serum of COVID-19 patients lowers the expression of Paired-Box-Protein-Pax-5 (PAX5), a master regulator of B-cell survival, proliferation and differentiation, in both human and mouse pre-B-cells, while the PGE2 inhibitor taxifolin directly reduces SARS-CoV-2-induced PGE2 production and attenuates viral replication. Risk-factors for severe disease courses, i.e. older age, male sex and air pollution are associated with higher PGE2 production and lower PAX5 expression in pre-B-cells. Since PGE2 acts broadly immunosuppressive its elevation might reduce the early anti-viral defense and its inhibition may therefore reduce severe disease courses.

scholarly journals Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255335
Author(s):  
Melanie Ricke-Hoch ◽  
Elisabeth Stelling ◽  
Lisa Lasswitz ◽  
Antonia P. Gunesch ◽  
Martina Kasten ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
B Cell ◽  
Life Style ◽  
Severe Disease ◽  
Serum Levels ◽  
Regular Exercise ◽  
Sedentary Life ◽  
Male Sex ◽  
Cox 2 ◽  
Sedentary Life Style

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.

scholarly journals Marine Alga Ecklonia cava Extract and Dieckol Attenuate Prostaglandin E2 Production in HaCaT Keratinocytes Exposed to Airborne Particulate Matter

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 190 ◽  
Author(s):  
Jae Won Ha ◽  
Hyerim Song ◽  
Seong Su Hong ◽  
Yong Chool Boo
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Particulate Matter ◽  
Prostaglandin E2 ◽  
Pge2 Production ◽  
Ecklonia Cava ◽  
Epidermal Keratinocytes ◽  
Hacat Keratinocytes ◽  
Cox 2 ◽  
Cox 1

Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E2 (PGE2) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E2 synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E2 synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE2, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE2 production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE2 production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.

scholarly journals Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients

2021 ◽  
Author(s):  
Emily Toscano-Guerra ◽  
Monica Martinez-Gallo ◽  
Iria Arrese-Munoz ◽  
Anna Gine ◽  
Noelia Diaz ◽  
...  
Keyword(s):  
Severe Disease ◽  
Strong Association ◽  
Serum Testosterone ◽  
Blood Levels ◽  
Testosterone Levels ◽  
Precise Knowledge ◽  
Male Patients ◽  
Male Sex ◽  
Classical Monocytes

Infection with SARS-CoV-2 portends a broad range of outcomes, from a majority of asymptomatic cases or mild clinical courses to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty and co-morbidities such as obesity, diabetes or cardiovascular disease. A precise knowledge is still lacking of the molecular and biological mechanisms that may explain the association of severe disease with male sex. Here, we show that testosterone trajectories are highly accurate individual predictors (AUC of ROC = 0.928, p < 0.0001) of survival in male COVID-19 patients. Longitudinal determinations of blood levels of luteinizing hormone (LH) and androstenedione suggest an early modest inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by either full recovery in survivors or a peripheral failure in lethal cases. Moreover, failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and decrease of non-classical monocytes. The strong association of recovery or failure to reinstate testosterone levels with survival or death from COVID-19 in male patients is suggestive of a significant role of testosterone status in the immune responses to COVID-19.

scholarly journals Induction of Cyclooxygenase-2 Gene in Pancreatic β-Cells by 12-Lipoxygenase Pathway Product 12-Hydroxyeicosatetraenoic Acid

2002 ◽  
Vol 16 (9) ◽  
pp. 2145-2154 ◽  
Author(s):  
Xiao Han ◽  
Songyuan Chen ◽  
Yujie Sun ◽  
Jerry L. Nadler ◽  
David Bleich
Keyword(s):  
Gene Expression ◽  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Pge2 Production ◽  
Hydroxyeicosatetraenoic Acid ◽  
Lipoxygenase Inhibitor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cox 2 ◽  
12 Lipoxygenase

Abstract Cyclooxygenase-2 (COX-2) gene and 12-lipoxygenase (12-LO) gene are preferentially expressed over other types of cyclooxygenase and lipoxygenase in pancreatic β-cells. Inhibition of either COX-2 or 12-LO can prevent cytokine-induced pancreatic β-cell dysfunction as defined by inhibition of glucose-stimulated insulin secretion. As cellular stress induces both genes and their respective end products in pancreatic β-cells, we evaluated the role of 12-hydroxyeicosatetraenoic acid (HETE) on COX-2 gene expression, protein expression, and prostaglandin E2 (PGE2) production. We demonstrate that 12-HETE significantly increases COX-2 gene expression and consequent product formation, whereas a closely related lipid, 15-HETE, does not. In addition, IL-1β-stimulated prostaglandin E2 production is completely inhibited by a preferential lipoxygenase inhibitor cinnaminyl-3,4-dihydroxy-α-cyanocinnamate. We then evaluated IL-1β-induced PGE2 production in islets purified from control C57BL/6 mice and 12-LO knockout mice lacking cytokine-inducible 12-HETE. IL-1β stimulated an 8-fold increase in PGE2 production in C57BL/6 islets but failed to stimulate PGE2 in 12-LO knockout islets. Addition of 12-HETE to 12-LO knockout islet cells produced a statistically significant rise in PGE2 production. Furthermore, 12-HETE, but not 15-HETE, stimulated COX-2 promoter and activator protein-1 binding activity. These data demonstrate that 12-HETE mediates cytokine-induced COX-2 gene transcription and resultant PGE2 production in pancreatic β-cells.

Mikroglia und immunologische Mechanismen in der neuropsychiatrischen Forschung

2014 ◽  
Vol 33 (11) ◽  
pp. 761-770
Author(s):  
M. J. Schwarz ◽  
B. Leitner ◽  
E. Weidinger ◽  
N. Müller
Keyword(s):  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Cox 2

ZusammenfassungDie Psychoneuroimmunologie beschäftigt sich mit den Wechselwirkungen zwischen der (gesunden) Psyche, psychischen Störungen und dem Immunsystem. Inzwischen hat sich gezeigt, dass zumindest bei Subgruppen psychischer Störungen wie Schizophrenie und Depression ein entzündlicher Prozess bei der Pathogenese eine Rolle spielt. Da für Schizophrenie und Depression auf diesem Gebiet die meisten Befunde vorliegen, konzentriert sich diese Übersicht auf diese beiden Störungsbilder. Die differenzielle Aktivierung von Mikrogliazellen und Astrozyten als funktionelle Träger des Immunsystems im ZNS, trägt zur Typ-1/Typ-2-Inbalance bei. Das entzündliche Geschehen ist verbunden mit höherer Prostaglandin-E2 (PGE-2)-Produktion und erhöhter Cyclooxygenase-2 (COX-2)-Expression. Zunehmende Evidenz aus klinischen Studien mit COX-2-Inhibitoren weisen auf einen günstigen Effekt antiinflammatorischer Therapie bei Schizophrenie hin, speziell in frühen Stadien der Krankheit. Sowohl bei Depression als auch bei Schizophrenie ist die Vulnerabilitäts- Stress-Hypothese weitgehend akzeptiert. So zeigte sich z. B. dass – bei entsprechender genetischer Disposition – Stress im frühen Lebensalter oder Separationsstress mit einem Anstieg proinflammatorischer Zytokine einhergehen und zu einer Immunaktivierung führen. Die Interaktionen zwischen dem Immunsystem, Neurotransmittern und dem Tryptophan- Kynurenin-System sind entscheidende Komponenten für die Pathogenese von Stress und Depression. Eine antientzündliche Behandlung, z. B. mit dem COX-2-Inhibitor Celecoxib, zeigt antidepressive Effekte.

Inflammatorische Prozesse in der Pathogenese psychischer Störungen

2010 ◽  
Vol 7 (03) ◽  
pp. 154-161
Author(s):  
M. Schwarz ◽  
N. Müller
Keyword(s):  
Prostaglandin E2 ◽  
Cox 2 ◽  
Inflammatorische Prozesse

ZusammenfassungEin entzündliches Geschehen wird sowohl in der Pathogenese der Schizophrenie, als auch der Depression postuliert. Dies wird einschließlich möglicher therapeutischer Effekte einer antientzündlichen Therapie in diesem Artikel diskutiert. Unterschiedliche Mechanismen, die in der Aktivierung des Enzyms Indoleamin-2,3-dioxygenase (IDO) und im Tryptophan-Kynurenin-Metabolismus liegen und zu einem Anstieg der Kynureninsäure bei Schizophrenie und wahrscheinlich von Quinolinsäure bei Depression führen, spielen vermutlich eine Schlüsselrolle bei diesen Erkrankungen. Diese Unterschiede gehen mit einer Imbalance der glutaminergen Neurotransmission einher, die zu einem Übergewicht des N-methyl-D-aspartate-(NMDA-)Agonismus bei Depression und des NMDA-Antagonismus bei Schizophrenie führen. Die immunologische Imbalance resultiert sowohl bei Schizophrenie, als auch bei Depression in der erhöhten Produktion von Prostaglandin E2 (PE2) und wahrscheinlich auch in einer stärkeren Zyklooxygenase-2-(COX-2-)Expression. Obwohl es viele Evidenzen dafür gibt, dass Interaktionen des Immunsystems, der IDO, des serotonergen Systems und der glutamatergen Neurotransmissionn eine wichtige Rolle bei Schizophrenie und Depression spielen, müssen weitere Untersuchungen zur Rolle von Genetik, Krankheitsverlauf, Geschlecht, Psychopathologie etc. durchgeführt werden. Inzwischen liegen auch erste Hinweise auf therapeutische Effekte von anti-entzündlichen Therapien vor. Ergebnisse von Tierversuchen und vorläufigen klinischen Studien mit COX-2-Inhibitoren zeigen sich bei Schizophrenie und Depression gegenüber Placebo überlegen.

scholarly journals Bone Marrow Mesenchymal Stromal Cells on Silk Fibroin Scaffolds to Attenuate Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1433
Author(s):  
Ok-Hyeon Kim ◽  
Jun-Hyung Park ◽  
Jong-In Son ◽  
Ok-Ja Yoon ◽  
Hyun-Jung Lee
Keyword(s):  
Bone Marrow ◽  
Cecal Ligation ◽  
Biological Properties ◽  
Pge2 Production ◽  
Polymicrobial Sepsis ◽  
Control Surface ◽  
Related Factors ◽  
Cox 2 ◽  
Anti Inflammatory

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders.

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