摘要
Vogt-Koyanagi-Harada(VKH)综合征被认为是一种自身免疫性疾病,可能由对感染的异常反应引起的。通过微生物产品激活TLR信号通路,能引起炎症反应和适应性免疫。目前,我们正在研究VKH疾病发病机理中TLR的作用。我们发现,与对照组相比,TLR3和TLR4而非TLR2的表达使患有葡萄膜炎的VKH患者的单核细胞源的巨噬细胞(MDMs)数目显著增加。患有葡萄膜炎的VKH患者MDMs中IL-1β、IL-6、IL-8、TNF-α和活性氧(ROS)水平显著升高。活性氧活化剂或抑制剂可分别显著上调或下调IL-1β、IL-6、IL-8和TNF-α的生成。NLRP3炎性体下调可显著抑制IL-1β而非IL-6、IL-8和TNF-α的产生。与对照组相比,VKH患者MDMs中 p38和ERK1/2的磷酸化水平显著升高。抑制p38或ERK1/2可显著减少IL-1β、IL-6、IL-8和TNF-α的表达。结果表明,增加MDMs中TLR3/4的表达可能参与VKH疾病的发病机制,此发病机制可能通过升高活性氧水平介导的炎性细胞因子诱导产生。
关键词: 自身免疫,NLRP3炎性体,活性氧簇,Toll样受体,Vogt-Koyanagi- Harada(VKH)综合症。
Current Molecular Medicine
Title:TLR3 and TLR4 But not TLR2 are Involved in Vogt-Koyanagi- Harada Disease by Triggering Proinflammatory Cytokines Production Through Promoting the Production of Mitochondrial Reactive Oxygen Species
Volume: 15 Issue: 6
Author(s): L. Liang, X. Tan, Q. Zhou, Y. Tian, A. Kijlstra and P. Yang
Affiliation:
关键词: 自身免疫,NLRP3炎性体,活性氧簇,Toll样受体,Vogt-Koyanagi- Harada(VKH)综合症。
摘要: Vogt-Koyanagi-Harada (VKH) disease is considered to be an autoimmune disease possibly triggered by an abnormal response to infection. Activation of TLRs signaling pathways by microbial products can drive inflammatory responses and adaptive immunity. In the present study, we investigated the role of TLRs in the pathogenesis of VKH disease. We showed that the expression of TLR3 and TLR4, but not TLR2, was significantly increased in monocyte-derived macrophages (MDMs) from VKH patients with active uveitis compared to controls. VKH patients with active uveitis showed an elevated level of IL-1β, IL-6, IL-8, TNF-α and reactive oxygen species (ROS) in MDMs. IL-1β, IL-6, IL-8 and TNF-α production could be significantly upregulated and downregulated by a ROS activator or inhibitor, respectively. Downregulation of the NLRP3 inflammasome significantly inhibited the production of IL-1β but not IL-6, IL-8 and TNF-α. The phosphorylation levels of p38 and ERK1/2 were significantly higher in MDMs from active VKH patients compared to controls. Inhibition of p38 or ERK1/2 significantly decreased IL-1β, IL-6, IL-8 and TNF-α expression. These results suggest that the increased expression of TLR3/4 in MDMs may be involved in the pathogenesis of VKH disease by the induction of inflammatory cytokines which is mediated by enhanced production of ROS.
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Cite this article as:
L. Liang, X. Tan, Q. Zhou, Y. Tian, A. Kijlstra and P. Yang , TLR3 and TLR4 But not TLR2 are Involved in Vogt-Koyanagi- Harada Disease by Triggering Proinflammatory Cytokines Production Through Promoting the Production of Mitochondrial Reactive Oxygen Species, Current Molecular Medicine 2015; 15 (6) . https://dx.doi.org/10.2174/1566524015666150731095611
DOI https://dx.doi.org/10.2174/1566524015666150731095611 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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