Mitochondrial-targeted ubiquinone alleviates concanavalin A-induced hepatitis via immune modulation.

Autor: Desta YT; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China., Wu M; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China., Bai L; Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, 230027 Hefei, China., Wu X; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China., Xiong M; Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China. Electronic address: karren126@126.com., Weng X; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China. Electronic address: wengxiufang@hust.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2020 Jul; Vol. 84, pp. 106518. Date of Electronic Publication: 2020 May 05.
DOI: 10.1016/j.intimp.2020.106518
Abstrakt: Background: Despite knowledge regarding the effects of antioxidants in ameliorating oxidative damage, evidence concerning their effects on activated immune cells is lacking. Here, a concanavalin A (Con A)-induced hepatitis mouse model was used to investigate the protective effects and immune regulatory mechanisms of mitochondrial-targeted ubiquinone (MitoQ).
Methods: Wild-type (WT) and CD1d-knockout (CD1d -/- , NKT cell deficient) mice were pretreated with MitoQ and then intravenously injected with a sublethal dose of Con A. Serum transaminase and inflammatory cytokine levels were tested. Immune cell functions and AMPK/mTORC1 pathway activation in liver tissue were also evaluated.
Results: NKT cells were critical for extensive pro-inflammatory cytokine production and prolonged liver injury upon Con A challenge, while IFN-γ-producing non-NKT cells played an important role during the hyperacute phase. MitoQ treatment not only ameliorated NKT cell-independent hyperacute hepatitis within 12 h post Con A administration but also alleviated NKT cell-dependent extended liver injury at 24 h. The underlying mechanisms involved an inhibition of the heightened activation of iNKT cells and conventional T cells, suppression of the excessive production of IFN-γ, TNF-α and IL-6, and modulation of aberrant AMPK and mTORC1 pathways.
Conclusion: MitoQ efficiently alleviates Con A-induced hepatitis through immune regulation, suggesting a new therapeutic approach for immune-mediated liver injury by targeting mitochondrial ROS.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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