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Toll-like receptor 10 controls TLR2-induced cytokine production in monocytes from patients with Parkinson's disease
Journal of Neuroscience Research ( IF 4.2 ) Pub Date : 2021-07-14 , DOI: 10.1002/jnr.24916
Hermínio Maurício da Rocha Sobrinho 1, 2 , Rodrigo Saar Gomes 1 , Delson José da Silva 3 , Valéria Bernadete Leite Quixabeira 1, 2 , Leo A B Joosten 4 , Cristina Ribeiro de Barros Cardoso 5 , Fátima Ribeiro-Dias 1
Affiliation  

Peripheral inflammation, particularly mediated by monocytes, can cause neuroinflammation in Parkinson's disease (PD). We investigated the mechanism of TLR2-induced cytokine impairment in peripheral monocytes from PD patients and the association between the presence of CD14+TLR10+ monocytes and PD severity. Peripheral blood mononuclear cells from PD patients and healthy individuals were evaluated for TLR expression on monocyte subsets (CD14 and CD16 expression) using flow cytometry. Moreover, cytokines were evaluated using flow cytometry after stimulation with Pam3Cys (TLR2/TLR1 agonist) in the absence or presence of neutralizing antibodies to TLR10. The severity of PD was assessed using the unified PD rating scale (UPDRS) and motor activity, anxiety (BAI), depression (BDI), and fatigue (PD Fatigue Scale-16) scales. The frequency of CD14+TLR10+ monocytes and expression intensity of TLR2 and TLR10 were higher in patients with PD than healthy individuals. The frequency of intermediate monocytes (CD14++CD16+) was not significantly increased in patients with PD, but was the main monocyte subset expressing TLR10. The TLR2/TLR1-impaired cytokine production (IL-6, TNFα, IL-8, and IL-10) in PD patients was reversed by neutralizing TLR10. The high frequency of total CD14+TLR10+ monocytes was associated with a reduction in the severity of PD according to the evaluation of motor and nonmotor symptoms. Peripheral monocytes from patients with PD showed phenotypic and functional alterations. The expression of TLR10 on monocytes can protect against PD by controlling TLR2-induced cytokine production. Furthermore, data suggested that a low frequency of CD14+TLR10+ monocytes indicates the severity of PD. The results identified new opportunities for the development of novel PD neuroprotective therapies.

中文翻译:

Toll 样受体 10 控制帕金森病患者单核细胞中 TLR2 诱导的细胞因子产生

外周炎症,特别是由单核细胞介导的炎症,可导致帕金森病 (PD) 中的神经炎症。我们研究了 PD 患者外周单核细胞中 TLR2 诱导的细胞因子损伤的机制以及 CD14 + TLR10 +单核细胞的存在与 PD 严重程度之间的关联。使用流式细胞术评估来自 PD 患者和健康个体的外周血单个核细胞在单核细胞亚群(CD14 和 CD16 表达)上的 TLR 表达。此外,在用 Pam 3刺激后,使用流式细胞仪评估细胞因子在不存在或存在针对 TLR10 的中和抗体的情况下,Cys(TLR2/TLR1 激动剂)。使用统一的 PD 评定量表 (UPDRS) 和运动活动、焦虑 (BAI)、抑郁 (BDI) 和疲劳 (PD Fatigue Scale-16) 量表评估 PD 的严重程度。PD患者CD14 + TLR10 +单核细胞的频率和TLR2、TLR10的表达强度高于健康个体。中间单核细胞(CD14 ++ CD16 +)的频率在 PD 患者中没有显着增加,而是表达 TLR10 的主要单核细胞亚群。通过中和 TLR10 可逆转 PD 患者中 TLR2/TLR1 受损的细胞因子产生(IL-6、TNFα、IL-8 和 IL-10)。总CD14 + TLR10的高频根据对运动和非运动症状的评估, +单核细胞与 PD 严重程度的降低有关。来自 PD 患者的外周单核细胞表现出表型和功能改变。TLR10 在单核细胞上的表达可以通过控制 TLR2 诱导的细胞因子产生来预防 PD。此外,数据表明 CD14 + TLR10 +单核细胞的低频率表明 PD 的严重性。结果确定了开发新型 PD 神经保护疗法的新机会。
更新日期:2021-07-14
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