Oxidative stress in the pathology and treatment of systemic lupus erythematosus.
Oxidative stress in the pathology and treatment of systemic lupus erythematosus.
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DOI：
10.1038/nrrheum.2013.147
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发表时间：
2013-11
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影响因子：
--
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--
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系统性红斑狼疮 (SLE) 中的氧化应激增加，导致免疫系统失调、细胞死亡信号异常激活和处理、自身抗体产生和致命合并症。 T 细胞中的线粒体功能障碍会促进高度扩散的炎症脂质氢过氧化物的释放，从而将氧化应激传播到其他细胞内细胞器并通过血流。自身抗原的氧化修饰会引发自身免疫，并且血清蛋白的这种修饰程度与 SLE 的疾病活动度和器官损伤显着相关。在 SLE 患者和该疾病动物模型的 T 细胞中，主要的细胞内抗氧化剂谷胱甘肽被耗尽，丝氨酸/苏氨酸蛋白激酶 mTOR 经历氧化还原依赖性激活。反过来，通过应用谷胱甘肽的氨基酸前体 N-乙酰半胱氨酸来逆转谷胱甘肽的消耗，可以改善狼疮易发小鼠的疾病活动性。针对 SLE 患者的试点研究已取得积极成果，值得进一步研究。可以想象，阻断 T 细胞中的 mTOR 激活可以为 B 细胞阻断和传统免疫抑制治疗提供一种耐受性良好且廉价的替代方法。然而，自身反应性 T 细胞、B 细胞和吞噬细胞中的区室化氧化应激可能有助于限制自身免疫，而抑制它可能是有害的。抗氧化疗法也可能有助于减轻其他治疗造成的损伤。因此，本综述旨在严格评估氧化应激的复杂性及其与 SLE 发病机制和治疗的相关性。
Oxidative stress is increased in systemic lupus erythematosus (SLE), and it contributes to immune system dysregulation, abnormal activation and processing of cell-death signals, autoantibody production and fatal comorbidities. Mitochondrial dysfunction in T cells promotes the release of highly diffusible inflammatory lipid hydroperoxides, which spread oxidative stress to other intracellular organelles and through the bloodstream. Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE. In T cells from patients with SLE and animal models of the disease, glutathione, the main intracellular antioxidant, is depleted and serine/threonine-protein kinase mTOR undergoes redox-dependent activation. In turn, reversal of glutathione depletion by application of its amino acid precursor, N-acetylcysteine, improves disease activity in lupus-prone mice; pilot studies in patients with SLE have yielded positive results that warrant further research. Blocking mTOR activation in T cells could conceivably provide a well-tolerated and inexpensive alternative approach to B-cell blockade and traditional immunosuppressive treatments. Nevertheless, compartmentalized oxidative stress in self-reactive T cells, B cells and phagocytic cells might serve to limit autoimmunity and its inhibition could be detrimental. Antioxidant therapy might also be useful in ameliorating damage caused by other treatments. This Review thus seeks to critically evaluate the complexity of oxidative stress and its relevance to the pathogenesis and treatment of SLE.
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DOI：
10.1074/jbc.m112.415992
发表时间：
2013-01-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Crabtree MJ;Brixey R;Batchelor H;Hale AB;Channon KM
通讯作者：
Channon KM
影响因子：
64.8
作者：
Chen, Chun-An;Wang, Tse-Yao;Varadharaj, Saradhadevi;Reyes, Levy A.;Hemann, Craig;Talukder, M. A. Hassan;Chen, Yeong-Renn;Druhan, Lawrence J.;Zweier, Jay L.
通讯作者：
Zweier, Jay L.
影响因子：
2.6
作者：
Avalos, I.;Chung, C. P.;Stein, C. M.
通讯作者：
Stein, C. M.
影响因子：
1.9
作者：
Angelica Sinicato, Nailu;da Silva Cardoso, Priscila Aparecida;Appenzeller, Simone
通讯作者：
Appenzeller, Simone
影响因子：
4.8
作者：
Banki, K;Hutter, E;Perl, A
通讯作者：
Perl, A