Decreased expression of A20 is associated with ocular Behcet's disease (BD) but not with Vogt- Koyanagi-Harada (VKH) disease
Decreased expression of A20 is associated with ocular Behcet's disease (BD) but not with Vogt- Koyanagi-Harada (VKH) disease
复制标题
A20 表达降低与眼部白塞氏病 (BD) 相关，但与沃格特-小柳-原田 (VKH) 病无关。
DOI：
10.1136/bjophthalmol-2017-311707
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发表时间：
2018-08-01
影响因子：
4.1
通讯作者：
Yang, Peizeng
中科院分区：
文献类型：
--
作者：
He, Yue;Wang, Chaokui;Yang, Peizeng
目的A20是一种广泛表达和诱导的胞浆蛋白，在炎症和免疫的负性调节中发挥重要作用。本研究探讨A20在白塞病(BD)和Vogt-Koyanagi Harada病(VKH)中的作用。方法采用实时荧光定量聚合酶链式反应(Real-Time-PCR)检测BD伴活动期和非活动期葡萄膜炎、VKH伴活动期和非活动期葡萄膜炎患者外周血单个核细胞(PBMC)和树突状细胞(DC)中A20水平。通过携带A20 shRNA载体的腺病毒转导DC，实现A20沉默的效果。流式细胞仪检测A20沉默对DC成熟的影响。用ELISA法分析A20沉默DC对DC和CD4(+)T细胞产生细胞因子的影响。结果BD活动期葡萄膜炎患者PBMC和DC中A20的表达明显低于正常对照组，而VKH患者的PBMC和DC中A20的表达无明显变化。沉默A20可显著提高IL-1β和IL-6水平，抑制抗炎细胞因子IL-10和IL-27的表达。A20的下调也导致了CD4(+)T细胞产生IL-17的增加。但下调DC表面A20表达对CD40、CD80、CD83、CD86和HLA-DR等细胞表面标志物无明显影响。沉默A20导致磷酸化JNK和磷酸化MAPK p38的表达增加，但不影响磷酸化ERK1/2的表达。结论A20在BD活动期葡萄膜炎患者中表达降低，而在VKH病中不表达。A20的表达降低可能导致促炎细胞Th17的激活增强，从而导致BD的重新激活。
Purpose A20 is a ubiquitously expressed and Inducible cytosolic protein, which plays an important role in the negative regulation of inflammation and immunity. In this study, we investigated the role of A20 in Behcet's disease (BD) and Vogt-KoyanagiHarada (VKH) disease.Methods The levels of A20 in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were detected in BD patients with active and inactive uveitis, VKH patients with active and inactive uveitis, and normal subjects, respectively, by real-time PCR. The effect of A20 silencing was performed by transduction of DCs with adenovirus containing an A20 shRNA vector. The effect of A20 silencing on the maturation of DCs was measured by flow cytometry. The effect of A20 silencing of DCs on cytokine production by DCs and CD4(+) T cells was analysed by ELISA. The phosphorylation levels of .INK, p38 and ERK1/2 were detected by flow cytometry.Results The expression of A20 was markedly decreased in PBMCs and DCs obtained from BD patients with active uveitis, but not in patients with VKH disease as compared with normal controls. Silencing of A20 significantly increased the levels of interleukin (IL)-1 beta and IL-6 and suppressed the expression of the anti-inflammatory cytokines IL-10 and IL-27. Downregulation of A20 also led to an increase in IL-17 production by CD4(+) T cells. However, downregulation of A20 in DCs did not have an effect on cell surface markers such as CD40, CD80, CD83, CD86 and HLA-DR. Silencing of A20 caused an increased expression of phospho-JNK and phospho-MAPK p38 but not phospho-ERK1/2.Conclusions This study showed that the expression of A20 was decreased in BD patients with active uveitis but not in VKH disease. Decreased expression of A20 may lead to an enhanced activation of proinflammatory Th17 cells, causing a reactivation of BD.