白细胞介素-25对白细胞介素-17A促类风湿关节炎滑膜成纤维细胞细胞外调节蛋白激酶1/2和MMP-3表达的拮抗作用的研究  

The inhibition of interleukin-25 on the effect of interleukin-17 for ERK1/2 and matrix metalloprotei-3 in rheumatoid arthritis fibroblast-like synoviocytes

作　　者：鲁锦玥 达明莲 封昱辰 康国荣 张慧[1] 沈海丽[1] Lu Jinyue;Da Minglian;Feng Yuchen;Kang Guorong;Zhang Hui;Shen Haili(Department of Rheumatology,Second Hospital of Lanzhou University,Gansu 730000, China)

机构地区：[1]兰州大学第二医院风湿免疫科,730000

出　　处：《中华风湿病学杂志》2018年第12期820-823,共4页Chinese Journal of Rheumatology

基　　金：兰州市科技局项目(2017-4-89);兰州大学第二医院博士科研基金(ynbskyjj2015-1-14);兰州大学第二医院萃英研究生指导教师培育计划.

摘　　要：目的研究分析IL-25对RA滑膜成纤维细胞(FLS)分化的影响以及对细胞外调节蛋白激酶(ERK)和MMP-3表达中的作用。方法培养RA和健康人FLS并鉴定,检测二者间ERK1/2和MMP-3蛋白的差异。RA-FLS分别用IL-17A(10 ng/ml)、不同浓度的IL-25(0.01、0.1、1和10 ng/ml)与IL-17A(10 ng/ml)共刺激24 h,蛋白质印迹法检测不同组间ERK1/2和MMP-3蛋白表达。不同组间独立样本t检验。 结果ERK1/2蛋白在RA-FLS中表达(1.71±0.17)高于健康人滑膜细胞(0.50±0.15),差异具有统计学意义(t=-9.13,P<0.01)。同时,MMP-3蛋白在RA-FLS中表达(0.50±0.13)高于健康人滑膜细胞(0.17±0.05),差异具有统计学意义(t=-4.10,P<0.05)。RA-FLS在IL-17A刺激后ERK1/2蛋白(0.77±0.22)和MMP-3蛋白(0.59±0.13)表达较无刺激组(0.18±0.35、0.04±0.03)增强,差异具有统计学意义(t=-4.69,P<0.01和t=-7.47,P<0.01),且随共刺激中IL-25浓度的增加能部分抑制IL-17A对RA-FLS中ERK1/2蛋白(0.54±0.26、0.48±0.18、0.48±0.23、0.23±0.06)和MMP-3蛋白(0.58±0.09、0.59±0.14、0.21±0.04、0.04±0.02)的刺激,差异有统计学意义(t=4.22,P<0.05;t=4.95,P<0.01;t=7.47,P<0.01)。结论IL-25可部分抑制IL-17A对RA-FLS中ERK1/2和MMP-3蛋白的刺激,可能通过此途径参与RA的发展,可作为IL-17A治疗RA的新靶点。Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibro-blast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls, then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01, 0.1, 1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively. The expression of ERK1/2 and MMP-3 protein was detected by the Western blot. T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15, 0.17±0.05) (t=-9.13, P<0.01 and t=-4.10, P<0.05), after stimulated with IL-17A, the expression of ERK1/2(0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35, 0.04±0.03) (t=-4.69, P<0.01 and t=-7.47, P<0.01). With increase of the con-centration on IL-25, the level of ERK1/2 (0.54±0.26, 0.48±0.18, 0.48±0.23, 0.23±0.06) and MMP-3 (0.58±0.09, 0.59±0.14, 0.21±0.04, 0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22, P<0.05 and t=4.95, P<0.01 and t=7.47, P<0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally, which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.

关 键 词：关节炎 类风湿 成纤维细胞 白细胞介素25 白细胞介素17A 细胞外调节蛋白激酶1/2 基质金属蛋白酶-3 

分 类 号：R593.22[医药卫生—内科学]