The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment
Abstract
:1. Introduction
2. The Production of ROS in Synovitis
3. ROS and Synovium Stromal Cells
3.1. The Role of ROS in FLSs
3.1.1. The Role of ROS-Induced Gene Mutations in FLSs
3.1.2. The Role of ROS-Related Autophagy and Apoptosis in FLSs
3.2. The Role of ROS in MLS
3.3. The Role of ROS in ECs
4. ROS and Synovial Immune Cells
4.1. The Role of ROS in Neutrophils
4.2. The Role of ROS in T Cells
4.3. The Role of ROS in B Cells
5. Targeted ROS Therapy for RA
5.1. Antioxidant Therapy
5.2. Oxidant-Promoting Therapy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Extracts/Monomers/Chemicals | Cells | Tissues/Animal Model | Dose/Concentration | Results | Potential Pathways | References |
---|---|---|---|---|---|---|
Hypericin photodynamic therapy | MH7A | / | 0.25–4 μM | Induced apoptosis; increased intracellular ROS; cleaved caspase 9, increased PARP; decreased NF-κB. | Mitochondrial apoptosis pathway, the death receptor pathway, NF-κB pathways | [196] |
Hempseed oil | MH7A | / | 1–2% | Promoted apoptosis; Increased intracellular ROS; up-regulating CHOP, GRP94 and GRP78; activated PARP. | ER stress-mediated apoptosis | [197] |
Brazilin | RAFLS | / | 10, 25 μg/mL | Increased autophagosome, LC3-II, intracellular ROS; inhibited NF-κB, reduced IL-6, IL-8. | Autophagic, NF-κB pathways | [72] |
Shikonin | RAFLS | AA | 2, 2.5, 3 μM; 1, 2 mg/kg/day, i g | Increased ROS, LC3-II/LC3-I, apoptosis; decreased ATP, TNF-α, IL-6, IL-1β, IL-8, IL-17A, and IL-10; upregulating Bax, caspase 3; downregulating Bcl-2. | Mitochondrial apoptosis pathway and PI3K-AKT-mTOR pathways | [198] |
Icariin | RAFLS | / | 0.1, 0.5, 1, 2.5, 5 μM | Inhibited migration, proliferation; induced G2/M phase arrest, apoptosis; increased Bax, activated- caspase 3, cleaved-PARP, Cyt-C, ROS; decreased Bcl-2, p p65, IκBα; MCMP (Δψm). | G2/M phase arrest; mitochondrial apoptosis pathway and NF-κB pathway | [199] |
Oridonin | RAFLS | / | 5, 10, 25, 40 μM | Triggered cell apoptosis; increased caspase 3, caspase 9, PARP, Cyt-C, ROS; inhibited p ERK1/2, p JNK1/2, MCMP (Δψm). | Mitochondrial apoptosis pathway | [200] |
α-Mangostin | MH7A/RAFLS | / | 10–100 μM | Promoted apoptosis; increased Cyt-C, ROS, caspase 3, caspase 9, p ERK1/2. Decreased MCMP (Δψm). | Mitochondrial apoptosis pathway, ERK1/2 signaling pathway | [201,202] |
Apigenin | RAFLS | / | 100 μM | Induced apoptotic pathway; activated MAPK, ERK1/2, caspase 3, caspase 7; increased intracellular ROS. | ERK1/2 signaling pathway, apoptosis pathway | [203] |
Eupatorium japonicum Thunb | RAFLS | / | 37.5 μg/mL | Induced apoptosis, ATF4, CHOP; decreased NF-κB, p38, IL-1β, MMP-9. | ER stress-mediated apoptosis, NF-κB pathway | [204] |
Cryptotanshinone | MH7A/RAFLS | / | 5 μM | Increased ROS; downregulated Bcl 2, p Akt p STAT3; upregulated Bad, caspase 3, PARP, p p38, p c Jun N-terminal kinase. | Akt, MAPK, STAT3 pathways, mitochondrial apoptosis pathway | [205] |
β-Elemene | RAFLS | / | 10–200 μg/mL | Promoted apoptosis; decreased MCMP (Δψm); increased Cyt-C, ROS, caspase 9, caspase 3, p p38 MAPK. | Mitochondrial apoptosis pathway, MAPK pathway | [206] |
1,7-Dihydroxy-3,4-dimethoxyxanthone | RAFLS | / | 8.7, 17.4, 34.7 μM | Upregulated GADD45α, p-p38; increased apoptosis, ROS; inhibited NF-κB. | NF-κB/p38 pathway, apoptosis pathway | [207] |
Scopoletin | rFLS (AIA) | / | 250, 500, 1000 µM | Upregulated Bax, caspase 3; decreased MCMP (Δψm), Bcl-2, NF-κB. | Mitochondrial apoptosis pathway, NF-κB pathway | [208] |
Resveratrol | RAFLS | / | 40, 80, 160, 320 μM | Downregulated Bcl-2, Atg5, LC3B; increased ROS; released Ca2+. | Mitochondrial apoptosis pathway and autophagy | [73] |
Sulforaphane | RA-T cell | / | 0.5, 1, 2.5, 5, 10 μM | Inhibited CD25/CD69, proliferation; increased intracellular ROS, decreased GSH, p STAT3, RORγt, IL-17A, IL-17F, IL-22. | STAT3 signaling | [169] |
Extracts/Monomers/Chemicals | Cells | Tissues/Animal Model | Dose/Concentration | Results | Potential Pathways | References |
---|---|---|---|---|---|---|
Suberoylanilide hydroxamic acid | RAFLS | / | 0.5–10 μM | Induced apoptotic pathway; increased intracellular ROS, total IκBα; decreased p IκBα, NF-κB p65, Bcl-xL, Mcl-1. | Apoptosis pathway, NF-κB pathways | [209] |
Niclosamide | RAFLS | / | 0.25, 0.5, 1 μM | Induced apoptotic pathway; increased intracellular ROS, Bax, Cyt-C, caspase 9, caspase 3; Decreased p Akt, Bcl-2. | Mitochondrial apoptosis pathway, Akt pathways | [210] |
Mitomycin C | RAFLS | / | 10, 25, 50, 100 μg/mL | Induced apoptosis; increased intracellular ROS, Cyt-C, Bax/Bcl-2, caspase 9, caspase 3, PARP; decreased MCMP (Δψm). | Mitochondrial apoptosis pathway | [211] |
Menadione | CD4 naive (CD4+CD45RO−) T cell | Human synovial tissue-NSG chimaera | 3 μM; 10 mg/kg/day, i g | Increased ROS, p ATM, T-bet, RORγ; decreased IFN-γ, IL-17, TNF-α, IL-1β, IL-6, RANKL; inhibited spontaneous hypermobility. | ATM signaling | [161] |
Buthionine sulfoximine | / | Human synovial tissue-NSG chimaera | 1000 mg/kg/day, i g | Increased intracellular ROS; decreased IFN-γ, IL-17, TNF-α, IL-1β, IL-6, RANKL, GSH, T-bet, RORγ; inhibited spontaneous hypermobility | ATM signaling | [161] |
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Wang, X.; Fan, D.; Cao, X.; Ye, Q.; Wang, Q.; Zhang, M.; Xiao, C. The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment. Antioxidants 2022, 11, 1153. https://doi.org/10.3390/antiox11061153
Wang X, Fan D, Cao X, Ye Q, Wang Q, Zhang M, Xiao C. The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment. Antioxidants. 2022; 11(6):1153. https://doi.org/10.3390/antiox11061153
Chicago/Turabian StyleWang, Xing, Danping Fan, Xiaoxue Cao, Qinbin Ye, Qiong Wang, Mengxiao Zhang, and Cheng Xiao. 2022. "The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment" Antioxidants 11, no. 6: 1153. https://doi.org/10.3390/antiox11061153
APA StyleWang, X., Fan, D., Cao, X., Ye, Q., Wang, Q., Zhang, M., & Xiao, C. (2022). The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment. Antioxidants, 11(6), 1153. https://doi.org/10.3390/antiox11061153