Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity.
SARS-CoV-2
cytokines
human lung adenocarcinoma A549 cells
necroptosis
nicotine
poly(I:C)
proinflammatory cytokines
pyroptosis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Aug 2022
22 Aug 2022
Historique:
received:
26
07
2022
revised:
12
08
2022
accepted:
19
08
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
The aims of our study are to: (i) investigate the ability of nicotine to modulate the expression level of inflammatory cytokines in A549 cells infected with SARS-CoV-2; (ii) elucidate the ultrastructural features caused by the combination nicotine+SARS-CoV-2; and (iii) demonstrate the mechanism of action. In this study, A549 cells pretreated with nicotine were either exposed to LPS or poly(I:C), or infected with SARS-CoV-2. Treated and untreated cells were analyzed for cytokine production, cytotoxicity, and ultrastructural modifications. Vero E6 cells were used as a positive reference. Cells pretreated with nicotine showed a decrease of IL6 and TNFα in A549 cells induced by LPS or poly(I:C). In contrast, cells exposed to SARS-CoV-2 showed a high increase of IL6, IL8, IL10 and TNFα, high cytopathic effects that were dose- and time-dependent, and profound ultrastructural modifications. These modifications were characterized by membrane ruptures and fragmentation, the swelling of cytosol and mitochondria, the release of cytoplasmic content in extracellular spaces (including osmiophilic granules), the fragmentation of endoplasmic reticulum, and chromatin disorganization. Nicotine increased SARS-CoV-2 cytopathic effects, elevating the levels of inflammatory cytokines, and inducing severe cellular damage, with features resembling pyroptosis and necroptosis. The protective role of nicotine in COVID-19 is definitively ruled out.
Identifiants
pubmed: 36012747
pii: ijms23169488
doi: 10.3390/ijms23169488
pmc: PMC9409480
pii:
doi:
Substances chimiques
Cytokines
0
Interleukin-6
0
Lipopolysaccharides
0
Tumor Necrosis Factor-alpha
0
Nicotine
6M3C89ZY6R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Lancet. 2020 Feb 22;395(10224):565-574
pubmed: 32007145
Cell Rep. 2021 Apr 6;35(1):108959
pubmed: 33811811
Cell. 2018 May 3;173(4):920-933.e13
pubmed: 29576451
Front Cell Infect Microbiol. 2020 May 29;10:237
pubmed: 32547960
Cell Physiol Biochem. 2011;27(5):605-12
pubmed: 21691078
J Exp Med. 2021 Mar 1;218(3):
pubmed: 33231615
JCI Insight. 2020 Jul 9;5(13):
pubmed: 32544099
Front Immunol. 2021 Apr 02;12:661162
pubmed: 33868312
Eur Respir J. 2020 Jun 4;55(6):
pubmed: 32350104
JCI Insight. 2021 Sep 22;6(18):
pubmed: 34375313
Thorax. 2021 Jul;76(7):714-722
pubmed: 33402392
C R Biol. 2020 Jun 05;343(1):33-39
pubmed: 32720486
Nat Rev Immunol. 2021 Nov;21(11):694-703
pubmed: 34373622
Nat Med. 2020 Oct;26(10):1636-1643
pubmed: 32839624
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Tob Induc Dis. 2020 Dec 14;18:105
pubmed: 33328837
Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620933508
pubmed: 32539627
Eur Respir J. 2020 Jul 16;56(1):
pubmed: 32430431
Tob Use Insights. 2021 Dec 20;14:1179173X211068027
pubmed: 34987300
Molecules. 2020 Dec 28;26(1):
pubmed: 33379366
Front Cell Dev Biol. 2020 Sep 16;8:559841
pubmed: 33042994
Nat Commun. 2021 Aug 2;12(1):4664
pubmed: 34341353
Cytokine. 2008 May;42(2):145-151
pubmed: 18304834
Front Immunol. 2020 Jun 11;11:1359
pubmed: 32595653
Lancet Respir Med. 2021 Sep;9(9):937
pubmed: 34411510
Immunity. 2013 Jul 25;39(1):123-35
pubmed: 23871209
J Gen Virol. 2020 Sep;101(9):925-940
pubmed: 32568027
Int J Cancer. 1976 Jan 15;17(1):62-70
pubmed: 175022
Eur Respir J. 2020 Jun 4;55(6):
pubmed: 32341101
Am J Pathol. 2021 Jan;191(1):4-17
pubmed: 32919977
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
ERJ Open Res. 2021 Apr 12;7(2):
pubmed: 33850935
Nat Rev Mol Cell Biol. 2022 Jan;23(1):3-20
pubmed: 34611326
Acta Psychol (Amst). 2022 Feb;222:103458
pubmed: 34933210
Front Immunol. 2021 Nov 09;12:771609
pubmed: 34858428
Carcinogenesis. 2021 Aug 19;42(8):1009-1022
pubmed: 34223886
Aging (Albany NY). 2019 Dec 13;11(24):12810-12821
pubmed: 31835256
Am J Respir Cell Mol Biol. 2021 May;64(5):579-591
pubmed: 33625952
Cell. 2021 Jan 7;184(1):149-168.e17
pubmed: 33278357