A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.
A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.
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DOI：
10.1371/journal.pone.0086105
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hsieh SL
中科院分区：
文献类型：
--
作者：
Chen DY;Yao L;Chen YM;Lin CC;Huang KC;Chen ST;Lan JL;Hsieh SL
髓样DAP 12相关凝集素-1（MDL-1）和DAP 12在人类类风湿性关节炎（RA）中的致病作用尚不清楚。通过流式细胞术分析22例活动性RA患者、16例非活动性RA患者、12例骨关节炎（OA）患者和10例健康对照（HC）中MDL-1表达单核细胞的频率。采用定量PCR检测PBMCs上MDL-1和DAP 12的mRNA表达水平，免疫组化检测滑膜中MDL-1和DAP 12的蛋白表达水平。与非活动性RA患者（34.1%）、OA患者（27.9%）和HC（21.2%）相比，活动性RA患者（53.6%）中观察到循环MDL-1表达单核细胞的中位百分比显著更高。活动期RA患者PBMC中MDL-1和DAP 12基因表达水平及其滑膜中蛋白表达水平均显著高于非活动期RA或OA患者。MDL-1水平与疾病活动度、关节损伤和促炎细胞因子水平呈正相关。MDL-1激活剂（登革病毒2型抗原）对PBMC的刺激导致RA患者的促炎细胞因子水平显著高于OA患者或HC患者，表明MDL-1激活是功能性的。MDL-1表达单核细胞的频率和MDL-1和DAP 12基因表达水平在有效治疗后显著降低。MDL-1和DAP 12的一致过表达与RA患者促炎细胞因子的产生增加相关，表明它们在调节关节炎症中的作用。
The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.
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作者：
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