Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Reis, Mouzarllem Barros; Rodrigues, Fernanda Luciano; Lautherbach, Natália; Kanashiro, Alexandre; Sorgi, Carlos Artério; Meirelles, Alyne Fávero Galvão; Silva, Carlos A. A.; Zoccal, Karina Furlani; Souza, Camila Oliveira Silva; Ramos, Simone G.; Matsuno, Alessandra Kimie; Rocha, Lenaldo Branco; Salgado, Hélio César; Navegantes, Luiz Carlos Carvalho; Kettelhut, Ísis C.; Cupo, Palmira; Gardinassi, Luiz Gustavo; Faccioli, Lúcia Helena

doi:10.1038/s41467-020-19232-8

Cited by 31 publications

(47 citation statements)

References 51 publications

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“…In the present study, comparing AA, 5-HETE, 11-HETE, cytokine, and receptor expression demonstrated the absence of glucocorticoid effects. These results, in addition to the results of other studies from our laboratory 3 , suggest that glucocorticoids did not have an effect in our cohort. This was most likely due to the fact that treatment was started late, namely after inflammation has been triggered by infection.…”

Section: Discussionsupporting

confidence: 82%

“…Contrary to our expectations, glucocorticoids did not alter cytokine production (Table S7). As a result, we suggest that, regardless of whether Covid-19 is treated with glucocorticoids, cross-talk occurs between cytokines, lipid mediators, and ACh, as previously reported 2,3,91 . IL-1 induces 11-HETE 46 ; arterial relaxation induced by ACh is mediated by 11-HETE and is inhibited by indomethacin 43 .…”

Section: Discussionsupporting

confidence: 80%

“…IL-1 induces 11-HETE 46 ; arterial relaxation induced by ACh is mediated by 11-HETE and is inhibited by indomethacin 43 . In our studies on scorpion envenomation, ACh release was found to be mediated by PGE2-induced by IL-1 and inhibited by indomethacin 3 . In the present study, comparing AA, 5-HETE, 11-HETE, cytokine, and receptor expression demonstrated the absence of glucocorticoid effects.…”

Section: Discussionmentioning

confidence: 58%

“…Individuals Covid-19 may present asymptomatically or with manifestations ranging from acute respiratory distress syndrome to systemic hyperinflammation and organ failure, events attributed to cytokine storms 1 . Free polyunsaturated fatty acids, such as AA and derivative eicosanoids, regulate inflammation 2,3 , yet their role in Covid-19 has not been well investigated.…”

Section: Introductionmentioning

confidence: 99%

“…ACh, which is released by nerves 4 , leukocytes 5 , and airway epithelial cells 6 , regulates metabolism 7 , cardiac function 8 , airway inflammation 9 , and cytokine production 10 , all of which occur in Covid-19. It is known that eicosanoids stimulate ACh release 3 , but crosstalk between cholinergic and lipid mediator pathways in Covid-19 still need to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Cholinergic and lipid mediators crosstalk in Covid-19 and the impact of glucocorticoid therapy

Pérez

Pimentel

Fuzo

et al. 2021

Preprint

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Cytokine storms and hyperinflammation, potentially controlled by glucocorticoids, occur in COVID-19; the roles of lipid mediators and acetylcholine (ACh) and how glucocorticoid therapy affects their release in Covid-19 remain unclear. Blood and bronchoalveolar lavage (BAL) samples from SARS-CoV-2- and non-SARS-CoV-2-infected subjects were collected for metabolomic/lipidomic, cytokines, soluble CD14 (sCD14), and ACh, and CD14 and CD36-expressing monocyte/macrophage subpopulation analyses. Transcriptome reanalysis of pulmonary biopsies was performed by assessing coexpression, differential expression, and biological networks. Correlations of lipid mediators, sCD14, and ACh with glucocorticoid treatment were evaluated. This study enrolled 190 participants with Covid-19 at different disease stages, 13 hospitalized non-Covid-19 patients, and 39 healthy-participants. SARS-CoV-2 infection increased blood levels of arachidonic acid (AA), 5-HETE, 11-HETE, sCD14, and ACh but decreased monocyte CD14 and CD36 expression. 5-HETE, 11-HETE, cytokines, ACh, and neutrophils were higher in BAL than in circulation (fold-change for 5-HETE 389.0; 11-HETE 13.6; ACh 18.7, neutrophil 177.5, respectively). Only AA was higher in circulation than in BAL samples (fold-change 7.7). Results were considered significant at P<0.05, 95%CI. Transcriptome data revealed a unique gene expression profile associated with AA, 5-HETE, 11-HETE, ACh, and their receptors in Covid-19. Glucocorticoid treatment in severe/critical cases lowered ACh without impacting disease outcome. We first report that pulmonary inflammation and the worst outcomes in Covid-19 are associated with high levels of ACh and lipid mediators. Glucocorticoid therapy only reduced ACh, and we suggest that treatment may be started early, in combination with AA metabolism inhibitors, to better benefit severe/critical patients.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cholinergic and lipid mediators crosstalk in Covid-19 and the impact of glucocorticoid therapy

Pérez

Pimentel

Fuzo

et al. 2021

Preprint

Self Cite

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Polymeric Microspheres with High Mass Fraction of Therapeutics Enabled by the Manipulation of Kinetics Factor During Emulsion Droplet Solidification

Wei,

Zhu,

Morin

et al. 2024

Adv Funct Materials

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High drug‐loaded polymeric microspheres hold promise in biomedical fields due to reduced excipient administration, minimized side effects, and enhanced therapeutical efficacy. Although thermodynamic factors like drug‐carrier material compatibility are well‐known to influence the drug loading capacity of microspheres, they fail to explain the huge difference in drug loading degree observed for polymers and drugs with similar interactions. Here, based on the droplet microfluidic platform, the single droplet solidification process is investigated. The results indicated that amorphous polymers can hinder drug diffusion during droplet solidification compared to crystalline polymers, resulting in a higher drug loading degree. Next, this principle is applied to improve the drug loading capability of crystalline polymers (polycaprolactone (PCL) and poly(L‐lactide) (PLLA)) by random co‐polymerization (poly(caprolactone‐co‐L‐lactide) (PCL‐PLLA)), achieving 6.2–22.2 times increased drug loading degree. Moreover, PCL‐PLLA microspheres with a high content of indomethacin exhibited superior therapeutical efficacy in the treatment of gout arthritis. Overall, these results offer insights into the impact of polymer crystallization on droplet solidification kinetics, which consequently affects the drug loading capacity. These findings provide guidelines for the development of polymers for efficient drug encapsulation.

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Metabolomics-directed nanotechnology in viral diseases management: COVID-19 a case study

et al. 2023

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently regarded as the twenty-first century’s plague accounting for coronavirus disease 2019 (COVID-19). Besides its reported symptoms affecting the respiratory tract, it was found to alter several metabolic pathways inside the body. Nanoparticles proved to combat viral infections including COVID-19 to demonstrate great success in developing vaccines based on mRNA technology. However, various types of nanoparticles can affect the host metabolome. Considering the increasing proportion of nano-based vaccines, this review compiles and analyses how COVID-19 and nanoparticles affect lipids, amino acids, and carbohydrates metabolism. A search was conducted on PubMed, ScienceDirect, Web of Science for available information on the interrelationship between metabolomics and immunity in the context of SARS-CoV-2 infection and the effect of nanoparticles on metabolite levels. It was clear that SARS-CoV-2 disrupted several pathways to ensure a sufficient supply of its building blocks to facilitate its replication. Such information can help in developing treatment strategies against viral infections and COVID-19 based on interventions that overcome these metabolic changes. Furthermore, it showed that even drug-free nanoparticles can exert an influence on biological systems as evidenced by metabolomics. Graphical abstract

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Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Cited by 31 publications

References 51 publications

Cholinergic and lipid mediators crosstalk in Covid-19 and the impact of glucocorticoid therapy

Cholinergic and lipid mediators crosstalk in Covid-19 and the impact of glucocorticoid therapy

Polymeric Microspheres with High Mass Fraction of Therapeutics Enabled by the Manipulation of Kinetics Factor During Emulsion Droplet Solidification

Metabolomics-directed nanotechnology in viral diseases management: COVID-19 a case study

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