NLRP3 Inflammasome Is Activated in Fibromyalgia: The Effect of Coenzyme Q10

被引:85
作者
Cordero, Mario D. [1 ]
Alcocer-Gomez, Elisabet [1 ]
Culic, Ognjen [2 ]
Carrion, Angel M. [3 ]
de Miguel, Manuel [1 ]
Diaz-Parrado, Eduardo [1 ]
Perez-Villegas, Eva M. [3 ]
Bullon, Pedro [4 ]
Battino, Maurizio [5 ]
Antonio Sanchez-Alcazar, Jose [6 ,7 ]
机构
[1] Univ Seville, Fac Med, Dpto Citol & Histol Normal & Patol, E-41009 Seville, Spain
[2] Univ Zagreb, Fac Pharm & Biochem, Zagreb 41000, Croatia
[3] Univ Pablo de Olavide Sevilla, Div Neurociencias, Seville, Spain
[4] Univ Seville, Fac Odontol, Dept Periodontol, E-41009 Seville, Spain
[5] Univ Politecn Marche, Dipartimento Sci Clin Specialist & Odontostomatol, Sez Biochim, Ancona, Italy
[6] Univ Pablo de Olavide, CABD, CSIC Junta Andaluci, Seville, Spain
[7] ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Seville, Spain
关键词
MITOCHONDRIAL; DYSFUNCTION; IL-1-BETA; CORRELATE; SEVERITY;
D O I
10.1089/ars.2013.5198
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1169 / 1180
页数:12
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