Resolvin D1 and D2 reduce SARS-CoV-2-induced inflammatory responses in cystic fibrosis macrophages.
COVID-19
/ immunology
Cystic Fibrosis
/ immunology
Cytokines
/ immunology
Docosahexaenoic Acids
/ pharmacology
Female
Gene Expression Regulation
/ drug effects
Humans
Inflammation
/ immunology
Macrophages
/ immunology
Male
MicroRNAs
/ immunology
Pseudomonas Infections
/ immunology
Pseudomonas aeruginosa
/ immunology
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
COVID-19
resolution
respiratory viruses
specialized proresolving lipid mediators
ω-3 fatty acids
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:
04 2021
04 2021
Historique:
revised:
29
01
2021
received:
11
12
2020
accepted:
29
01
2021
entrez:
22
3
2021
pubmed:
23
3
2021
medline:
30
3
2021
Statut:
ppublish
Résumé
An excessive, non-resolving inflammatory response underlies severe COVID-19 that may have fatal outcomes. Therefore, the investigation of endogenous pathways leading to resolution of inflammation is of interest to uncover strategies for mitigating inflammation in people with SARS-CoV-2 infection. This becomes particularly urgent in individuals with preexisting pathologies characterized by chronic respiratory inflammation and prone to bacterial infection, such as cystic fibrosis (CF). Here, we analyzed the immune responses to SARS-CoV-2 virion spike 1 glycoprotein (S1) of macrophages (MΦ) from volunteers with and without CF and tested the efficacy of resolvins (Rv) D1 and D2 in regulating the inflammatory and antimicrobial functions of MΦ exposed to S1. S1 significantly increased chemokine release, including interleukin (IL)-8, in CF and non-CF MΦ, while it enhanced IL-6 and tumor necrosis factor (TNF)-α in non-CF MΦ, but not in CF cells. S1 also triggered the biosynthesis of RvD1 and modulated microRNAs miR-16, miR-29a, and miR-103, known to control the inflammatory responses. RvD1 and RvD2 treatment abated S1-induced inflammatory responses in CF and non-CF MΦ, significantly reducing the release of select chemokines and cytokines including IL-8 and TNF-α. RvD1 and RvD2 both restored the expression of miR-16 and miR-29a, while selectively increasing miR-223 and miR-125a, which are involved in NF-κB activation and MΦ inflammatory polarization. During Pseudomonas aeruginosa infection, S1 stimulated the MΦ phagocytic activity that was further enhanced by RvD1 and RvD2. These results provide a map of molecular responses to SARS-CoV-2 in MΦ, key determinants of COVID-19-related inflammation, unveiling some peculiarity in the response of cells from individuals with CF. They also demonstrate beneficial, regulatory actions of RvD1 and RvD2 on SARS-CoV-2-induced inflammation.
Identifiants
pubmed: 33749902
doi: 10.1096/fj.202001952R
pmc: PMC8250053
doi:
Substances chimiques
Cytokines
0
MicroRNAs
0
Spike Glycoprotein, Coronavirus
0
resolvin D1
0
resolvin D2
0
spike protein, SARS-CoV-2
0
Docosahexaenoic Acids
25167-62-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21441Subventions
Organisme : Cystic Fibrosis Foundation (CF Foundation)
ID : RECCHI19I0
Organisme : Cystic Fibrosis Foundation (CF Foundation)
ID : ROMANO19IO
Organisme : Cystic Fibrosis Foundation (CF Foundation)
ID : RECCHI20G1
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : L.548/93
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)
ID : Ex 60% (2019-2020)
Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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