Oral N-acetylcysteine decreases IFN-γ production and ameliorates ischemia-reperfusion injury in steatotic livers.
IFN-gamma
N-acetylcysteine (NAC)
NKT (natural killer T) cell
gadoxetate disodium
hepatic steatosis
ischemia-reperfusion injury (IRI)
liver transplantation
phasor-FLIM
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
17
03
2022
accepted:
11
07
2022
entrez:
23
9
2022
pubmed:
24
9
2022
medline:
28
9
2022
Statut:
epublish
Résumé
Type 1 Natural Killer T-cells (NKT1 cells) play a critical role in mediating hepatic ischemia-reperfusion injury (IRI). Although hepatic steatosis is a major risk factor for preservation type injury, how NKT cells impact this is understudied. Given NKT1 cell activation by phospholipid ligands recognized presented by CD1d, we hypothesized that NKT1 cells are key modulators of hepatic IRI because of the increased frequency of activating ligands in the setting of hepatic steatosis. We first demonstrate that IRI is exacerbated by a high-fat diet (HFD) in experimental murine models of warm partial ischemia. This is evident in the evaluation of ALT levels and Phasor-Fluorescence Lifetime (Phasor-FLIM) Imaging for glycolytic stress. Polychromatic flow cytometry identified pronounced increases in CD45+CD3+NK1.1+NKT1 cells in HFD fed mice when compared to mice fed a normal diet (ND). This observation is further extended to IRI, measuring
Identifiants
pubmed: 36148239
doi: 10.3389/fimmu.2022.898799
pmc: PMC9486542
doi:
Substances chimiques
Cytokines
0
Ligands
0
Peroxisome Proliferator-Activated Receptors
0
Phospholipids
0
Triglycerides
0
Interferon-gamma
82115-62-6
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
898799Subventions
Organisme : NIAID NIH HHS
ID : R21 AI130800
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK120521
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA051008
Pays : United States
Organisme : NIH HHS
ID : S10 OD025153
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK127830
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116567
Pays : United States
Informations de copyright
Copyright © 2022 Liggett, Kang, Ranjit, Rodriguez, Loh, Patil, Cui, Duttargi, Nguyen, He, Lee, Oza, Frank, Kwon, Li, Kallakury, Libby, Levi, Robson, Fishbein, Cui, Albanese, Khan and Kroemer.
Déclaration de conflit d'intérêts
Georgetown University filed a patent related to this manuscript. KK, WC, and AK are named as inventors on this application and declare that as a potential conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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