NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder
NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder
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DOI：
10.1016/j.bbi.2013.10.017
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发表时间：
2014-02-01
影响因子：
15.1
通讯作者：
Cordero, Mario D.
中科院分区：
文献类型：
--
作者：
Alcocer-Gomez, Elisabet;de Miguel, Manuel;Cordero, Mario D.
前言：重性抑郁障碍（MDD）是一种非常普遍的疾病，其发病机制至今仍不清楚。有一些假说和初步研究表明，细胞因子可能在MDD中发挥重要作用。在这方面，我们已经研究了NLRP 3炎性复合物的作用，在半胱天冬酶-1的成熟和加工的底物，IL-1 β和IL-18，在血细胞从MDD patients.Methods：40例MDD患者被选为这项研究，20个没有治疗和20个治疗与阿米替林，一种常见的三环类抗抑郁药。本研究包括来自20名健康志愿者的血液样本。采用Western blot和实时荧光定量PCR检测NLRP 3和caspase I的表达，以及血清IL-1 β和IL-18的水平。结果：未治疗组血细胞NLRP 3和caspase-1基因表达增加，血清IL-1 β和IL-18水平升高。IL-1 β和IL-18与MDD患者Beck抑郁量表（BDI）评分相关。有趣的是，阿米替林治疗降低了NLRP 3和caspase-1基因表达，以及IL-1 β和IL-18血清水平。由于已经确定氧化应激与NLRP 3炎性体活化相关，我们接下来研究了MDD患者中的线粒体ROS和脂质过氧化（LPO）水平。线粒体ROS和LPO水平的增加，观察到在MDD患者，但氧化损伤较高的MDD患者治疗阿米替林。结论：这些研究结果提供了新的见解MDD的发病机制和阿米替林治疗对NLRP 3炎性小体激活和IL-1 β和IL-18血清水平的影响。(C)2013 Elsevier Inc. All rights reserved.
Introduction: Major depressive disorder (MDD) is a very prevalent disease which pathogenic mechanism remains elusive. There are some hypotheses and pilot studies suggesting that cytokines may play an important role in MDD. In this respect, we have investigated the role of NLRP3 inflammasome complex in the maturation of caspase-1 and the processing of its substrates, IL-1 beta and IL-18, in blood cells from MDD patients.Methods: Forty MDD patients were selected for this study, twenty without treatments and twenty treated with amitriptyline, a common tricyclic antidepressant. Blood samples from twenty healthy volunteers were included in the study. The inflammasome activation was studied by Western blot and real-time PCR of NLRP3 and caspase I and serum levels of IL-1 beta and 18.Results: We observed increased gene expression of NLRP3 and caspase-1 in blood cells, and increased serum levels of IL-1 beta and IL-18 in non-treated patients. IL-1 beta and IL-18 correlated with Beck Depression Inventory (BDI) scores of MDD patients. Interestingly, amitriptyline treatment reduced NLRP3 and caspase-1 gene expression, and IL-1 beta and IL-18 serum levels. As it is well established that oxidative stress is associated with NLRP3 inflammasome activation, we next studied mitochondrial ROS and lipid peroxidation (LPO) levels in MDD patients. Increased levels of mitochondrial ROS and LPO were observed in MDD patients, however oxidative damage was higher in MDD patients treated with amitriptyline.Conclusions: These findings provide new insight into the pathogenesis of MDD and the effects of amitriptyline treatment on NLRP3 inflammasome activation and IL-1 beta and IL-18 serum levels. (C) 2013 Elsevier Inc. All rights reserved.