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Peripheral blood expression levels of inflammasome complex components in two different focal epilepsy syndromes
Journal of Neuroimmunology ( IF 2.9 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.jneuroim.2020.577343 Canan Ulusoy 1 , Ebru Nur Vanlı-Yavuz 2 , Elif Şanlı 1 , Özlem Timirci-Kahraman 3 , Vuslat Yılmaz 1 , Nerses Bebek 4 , Cem İsmail Küçükali 1 , Betül Baykan 4 , Erdem Tüzün 1
Journal of Neuroimmunology ( IF 2.9 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.jneuroim.2020.577343 Canan Ulusoy 1 , Ebru Nur Vanlı-Yavuz 2 , Elif Şanlı 1 , Özlem Timirci-Kahraman 3 , Vuslat Yılmaz 1 , Nerses Bebek 4 , Cem İsmail Küçükali 1 , Betül Baykan 4 , Erdem Tüzün 1
Affiliation
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BACKGROUND
Although the role of inflammation in epilepsy pathogenesis has been extensively investigated, the inflammasome complex, a key component of neuroinflammation, has been understudied in epilepsy patients. METHODS
To better understand the involvement of this system in epilepsy, levels of inflammasome complex components (NLRP1, NLRP3, CASP1, ASC), end-products of inflammasome complex activity [IL-1β, IL-18, nitric oxide synthase (NOS) isoforms] and other inflammatory factors (NFκB, IL-6, TNF-α) were measured in peripheral blood of patients with focal epilepsy of unknown cause (FEoUC) (n = 47), mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (n = 35) and healthy controls using real time qPCR and/or ELISA. RESULTS
Inflammasome complex associated factors were either downregulated or unchanged in epilepsy patients. Likewise, flow cytometry studies failed to show an increase in ratios of NLRP3-expressing CD3+ and CD14+ peripheral blood mononuclear cells (PBMC) in epileptic patients. Anti-neuronal antibody positive epilepsy patients showed increased NLRP1 and neuronal NOS mRNA expression levels, whereas patients under poly-therapy showed reduced serum inflammasome levels. FEoUC patients demonstrated increased PBMC NFκB mRNA expression levels and serum IL-1β and IL-6 levels. Both MTLE-HS and FEoUC patients displayed higher ratios of NFκB-expressing CD14+ PBMC than healthy controls. CONCLUSIONS
Although previous clinical studies have implicated increased inflammasome complex expression levels in epilepsy, our results indicate suppressed inflammasome complex activity in the peripheral blood of focal epilepsy patients. Alternatively, the IL-6-NFκB signaling pathway, appears to be activated in focal epilepsy, suggesting that factors of this pathway might be targeted for future theranostic applications.
中文翻译：
两种不同局灶性癫痫综合征中炎症小体复合成分的外周血表达水平
背景虽然炎症在癫痫发病机制中的作用已被广泛研究，但炎症小体复合物是神经炎症的关键组成部分，但在癫痫患者中的研究尚未充分。方法 为了更好地了解该系统在癫痫中的参与、炎症小体复合物成分（NLRP1、NLRP3、CASP1、ASC）的水平、炎症小体复合物活性的终产物 [IL-1β、IL-18、一氧化氮合酶 (NOS) 同种型] 和其他炎症因子（NFκB、IL-6、TNF-α）在不明原因局灶性癫痫（FEoUC）（n = 47）、颞叶内侧癫痫伴海马硬化（MTLE-HS）患者的外周血中检测(n = 35) 和使用实时 qPCR 和/或 ELISA 的健康对照。结果 炎症小体复合物相关因子在癫痫患者中下调或不变。同样地，流式细胞术研究未能显示癫痫患者中表达 NLRP3 的 CD3+ 和 CD14+ 外周血单核细胞 (PBMC) 的比率增加。抗神经元抗体阳性癫痫患者的 NLRP1 和神经元 NOS mRNA 表达水平升高，而接受多药治疗的患者血清炎性体水平降低。FEoUC 患者表现出增加的 PBMC NFκB mRNA 表达水平和血清 IL-1β 和 IL-6 水平。MTLE-HS 和 FEoUC 患者均显示出比健康对照更高的表达 NFκB 的 CD14+ PBMC 的比率。结论 尽管之前的临床研究表明癫痫中炎症小体复合物的表达水平增加，但我们的结果表明局灶性癫痫患者外周血中炎症小体复合物的活性受到抑制。或者，IL-6-NFκB 信号通路，
更新日期：2020-10-01
中文翻译：
两种不同局灶性癫痫综合征中炎症小体复合成分的外周血表达水平
背景虽然炎症在癫痫发病机制中的作用已被广泛研究，但炎症小体复合物是神经炎症的关键组成部分，但在癫痫患者中的研究尚未充分。方法 为了更好地了解该系统在癫痫中的参与、炎症小体复合物成分（NLRP1、NLRP3、CASP1、ASC）的水平、炎症小体复合物活性的终产物 [IL-1β、IL-18、一氧化氮合酶 (NOS) 同种型] 和其他炎症因子（NFκB、IL-6、TNF-α）在不明原因局灶性癫痫（FEoUC）（n = 47）、颞叶内侧癫痫伴海马硬化（MTLE-HS）患者的外周血中检测(n = 35) 和使用实时 qPCR 和/或 ELISA 的健康对照。结果 炎症小体复合物相关因子在癫痫患者中下调或不变。同样地，流式细胞术研究未能显示癫痫患者中表达 NLRP3 的 CD3+ 和 CD14+ 外周血单核细胞 (PBMC) 的比率增加。抗神经元抗体阳性癫痫患者的 NLRP1 和神经元 NOS mRNA 表达水平升高，而接受多药治疗的患者血清炎性体水平降低。FEoUC 患者表现出增加的 PBMC NFκB mRNA 表达水平和血清 IL-1β 和 IL-6 水平。MTLE-HS 和 FEoUC 患者均显示出比健康对照更高的表达 NFκB 的 CD14+ PBMC 的比率。结论 尽管之前的临床研究表明癫痫中炎症小体复合物的表达水平增加，但我们的结果表明局灶性癫痫患者外周血中炎症小体复合物的活性受到抑制。或者，IL-6-NFκB 信号通路，
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