NLRP3 Inflammasome Is Activated in Fibromyalgia: The Effect of Coenzyme Q10
NLRP3 Inflammasome Is Activated in Fibromyalgia: The Effect of Coenzyme Q10
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DOI：
10.1089/ars.2013.5198
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发表时间：
2014-03-10
影响因子：
6.6
通讯作者：
Antonio Sanchez-Alcazar, Jose
中科院分区：
文献类型：
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作者：
Cordero, Mario D.;Alcocer-Gomez, Elisabet;Antonio Sanchez-Alcazar, Jose
目的：纤维肌痛 (FM) 是一种常见的慢性疼痛综合征，其特征是全身痛觉过敏，并伴有疲劳和关节僵硬等多种症状。由于缺乏可靠的诊断生物标志物，FM 的诊断很困难，而治疗也很不充分。我们研究了辅酶 Q(10) (CoQ(10)) 缺乏和线粒体功能障碍在 FM 患者血细胞炎症小体激活中的作用，以及体外和体内 CoQ(10) 缺乏模型。结果：线粒体功能障碍伴随着白细胞介素（IL）-1、NLRP3（NOD样受体家族，含有pyrin结构域3）和caspase-1激活的蛋白表达增加，以及促炎细胞因子（IL-1和IL-18）血清水平的增加。对氨基苯甲酸酯治疗引起的血液单核细胞和小鼠 CoQ(10) 缺乏显示 NLRP3 炎性体激活并伴有明显的痛觉。一项针对 FM 患者的 CoQ(10) 安慰剂对照试验显示，NLRP3 炎性体激活以及 IL-1 和 IL-18 血清水平降低。创新：这些结果表明NLRP3炎症小体在FM发病机制中的重要作用，以及CoQ10控制炎症小体的能力。结论：这些发现为 FM 的发病机制提供了新的见解，并表明 NLRP3 炎性体抑制代表了该疾病的新治疗干预措施。抗氧化剂。氧化还原信号。 20、1169-1180。
Aims: Fibromyalgia (FM) is a prevalent chronic pain syndrome characterized by generalized hyperalgesia associated with a wide spectrum of symptoms such as fatigue and joint stiffness. Diagnosis of FM is difficult due to the lack of reliable diagnostic biomarkers, while treatment is largely inadequate. We have investigated the role of coenzyme Q(10) (CoQ(10)) deficiency and mitochondrial dysfunction in inflammasome activation in blood cells from FM patients, and in vitro and in vivo CoQ(10) deficiency models. Results: Mitochondrial dysfunction was accompanied by increased protein expression of interleukin (IL)-1, NLRP3 (NOD-like receptor family, pyrin domain containing 3) and caspase-1 activation, and an increase of serum levels of proinflammatory cytokines (IL-1 and IL-18). CoQ(10) deficiency induced by p-aminobenzoate treatment in blood mononuclear cells and mice showed NLRP3 inflammasome activation with marked algesia. A placebo-controlled trial of CoQ(10) in FM patients has shown a reduced NLRP3 inflammasome activation and IL-1 and IL-18 serum levels. Innovation: These results show an important role for the NLRP3 inflammasome in the pathogenesis of FM, and the capacity of CoQ10 in the control of inflammasome. Conclusion: These findings provide new insights into the pathogenesis of FM and suggest that NLRP3 inflammasome inhibition represents a new therapeutic intervention for the disease. Antioxid. Redox Signal. 20, 1169-1180.