Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS-CoV-2-infected mice.
Animals
Mice
Eicosanoids
/ metabolism
COVID-19
/ immunology
SARS-CoV-2
/ drug effects
Epoxide Hydrolases
/ antagonists & inhibitors
Cytokine Release Syndrome
/ drug therapy
COVID-19 Drug Treatment
Piperidines
/ pharmacology
Cytokines
/ metabolism
Humans
Lung
/ virology
Angiotensin-Converting Enzyme 2
/ metabolism
Disease Models, Animal
Phenylurea Compounds
/ pharmacology
Female
COVID‐19
SARS‐CoV‐2
cytokines
eicosanoids
soluble epoxide hydrolase
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
31 May 2024
31 May 2024
Historique:
revised:
01
04
2024
received:
29
10
2023
accepted:
10
05
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
24
5
2024
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves an initial viral infection phase followed by a host-response phase that includes an eicosanoid and cytokine storm, lung inflammation and respiratory failure. While vaccination and early anti-viral therapies are effective in preventing or limiting the pathogenic host response, this latter phase is poorly understood with no highly effective treatment options. Inhibitors of soluble epoxide hydrolase (sEH) increase levels of anti-inflammatory molecules called epoxyeicosatrienoic acids (EETs). This study aimed to investigate the impact of sEH inhibition on the host response to SARS-CoV-2 infection in a mouse model with human angiotensin-converting enzyme 2 (ACE2) expression. Mice were infected with SARS-CoV-2 and treated with either vehicle or the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU). At day 5 post-infection, SARS-CoV-2 induced weight loss, clinical signs, a cytokine storm, an eicosanoid storm, and severe lung inflammation with ~50% mortality on days 6-8 post-infection. SARS-CoV-2 infection induced lung expression of phospholipase A
Identifiants
pubmed: 38786655
doi: 10.1096/fj.202302202RR
doi:
Substances chimiques
Eicosanoids
0
Epoxide Hydrolases
EC 3.3.2.-
Piperidines
0
Cytokines
0
1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Phenylurea Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23692Subventions
Organisme : Intramural NIH HHS
ID : Z01 ES025034
Pays : United States
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI001281-04
Informations de copyright
© 2024 Federation of American Societies for Experimental Biology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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