Toll样受体2介导的与慢性移植物抗宿主病相关的干眼的NF-κB炎症反应。
Toll-like receptor 2-mediated NF-κB inflammatory responses in dry eye associated with cGVHD.
作者信息
He Chang, Lai Peilong, Weng Jianyu, Lin Shaoze, Wu Kaili, Du Xin, Liu Xialin
机构信息
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P R China.
出版信息
Mol Vis. 2011;17:2605-11. Epub 2011 Oct 5.
PURPOSE
Dry eye syndrome is one of the most common pathological manifestations in patients with chronic graft-versus-host disease (cGVHD). When dry eye occurs in association with cGVHD, the local inflammation is secondary to the systemic onset of inflammation. Toll-like receptor 2 (TLR2) signaling is thought to be essential for the inflammatory response and for immune disorders. The aim of this study was to explore whether the TLR2-mediated nuclear factor-kappa B (NF-κB) signaling pathway contributes to the inflammatory process of dry eye associated with cGVHD.
METHODS
Twenty patients with dry eye related to cGVHD and 20 controls were enrolled in this study. The patients with dry eye associated with cGVHD were diagnosed based on the clinical presentation and related ocular surface examinations such as Schirmer's test and fluorescein staining. In addition, dry eye symptom scoring (National Institutes of Health consensus criteria) and Ocular Surface Disease Index (OSDI) scoring were also evaluated in all patients. Peripheral blood was collected from the patients and the controls for subsequent experiments. mRNA levels of TLR2 and its downstream molecules, NF-κB and tumor necrosis factor (TNF)-α, were measured by quantitative Real-Time PCR (qRT-PCR). The protein level of TNF-α was detected by Enzyme-linked Immuno Sorbent Assay (ELISA).
RESULTS
TLR2 mRNA in the peripheral blood from patients with dry eye related to cGVHD increased significantly compared with the controls. NF-κB, the downstream target of TLR2, also showed a marked elevation. The mRNA and protein levels of TNF-α were significantly upregulated in these patients. Importantly, the TLR2 level was strongly correlated with the OSDI and the Schirmer's test (r=0.565, p=0.010<0.05; r=0.564, p=0.016<0.05) in dry eye related to cGVHD compared with the controls.
CONCLUSIONS
The TLR2-mediated NF-κB signaling pathway is activated in dry eye associated with cGVHD and contributes to the inflammatory state, which may predict the onset and progression of dry eye associated with cGVHD.
目的
干眼症是慢性移植物抗宿主病（cGVHD）患者最常见的病理表现之一。当干眼症与cGVHD相关联发生时，局部炎症继发于全身性炎症发作。Toll样受体2（TLR2）信号传导被认为对炎症反应和免疫紊乱至关重要。本研究的目的是探讨TLR2介导的核因子-κB（NF-κB）信号通路是否参与了与cGVHD相关的干眼症的炎症过程。
方法
本研究纳入了20例与cGVHD相关的干眼症患者和20例对照。与cGVHD相关的干眼症患者根据临床表现及相关眼表检查如泪液分泌试验和荧光素染色进行诊断。此外，还对所有患者进行了干眼症状评分（美国国立卫生研究院共识标准）和眼表疾病指数（OSDI）评分。采集患者和对照的外周血用于后续实验。通过定量实时聚合酶链反应（qRT-PCR）检测TLR2及其下游分子NF-κB和肿瘤坏死因子（TNF）-α的mRNA水平。通过酶联免疫吸附测定（ELISA）检测TNF-α的蛋白水平。
结果
与cGVHD相关的干眼症患者外周血中的TLR2 mRNA与对照相比显著增加。TLR2的下游靶点NF-κB也显著升高。这些患者中TNF-α的mRNA和蛋白水平均显著上调。重要的是，与对照相比，在与cGVHD相关的干眼症中，TLR2水平与OSDI及泪液分泌试验呈强相关性（r=0.565，p=0.010<0.05；r=0.564，p=0.016<0.05）。
结论
TLR2介导的NF-κB信号通路在与cGVHD相关的干眼症中被激活，并促成炎症状态，这可能预测与cGVHD相关的干眼症的发生和进展。
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