Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL- lpr mice
| Autor: | Fortner, Karen A, Blanco, Luz P, Buskiewicz, Iwona, Huang, Nick, Gibson, Pamela C, Cook, Deborah L, Pedersen, Hege L, Yuen, Peter S T, Murphy, Michael P, Perl, Andras, Kaplan, Mariana J, Budd, Ralph C |
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| Přispěvatelé: | Blanco, Luz P [0000-0002-8468-6518], Murphy, Michael P [0000-0003-1115-9618], Kaplan, Mariana J [0000-0003-2968-0815], Budd, Ralph C [0000-0001-8524-8758], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: | |
| Popis: | Funder: Central New York Community Foundation; FundRef: http://dx.doi.org/10.13039/100001026 Objectives: Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants. Methods: Lupus-prone MRL-lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function. Results: MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody . Conclusions: These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus. |
| Databáze: | OpenAIRE |
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