系统性红斑狼疮患者树突状细胞白细胞介素-12和干扰素-α表达与各亚型的关系

Study of the expression of interleukin-12 and interferon-α and their relationships with the dendritic cell subsets in systemic lupus erythematosus patients

目的诱导系统性红斑狼疮(SLE)患者外周血单核细胞分化树突状细胞(DC),检测DC分泌白细胞介素(IL)-12和干扰素(IFN)-α水平,并分析与DC各亚型的相关性,以了解树突状细胞在SLE疾病中的作用。方法联合应用粒细胞-巨噬细胞刺激因子(GM-CSF)、IL-4和肿瘤坏死因子(TNF)-α诱导分化DC成熟。酶联免疫吸附试验(ELISA)方法检测培养上清中IL-12和IFN-α表达,免疫荧光标记,流式细胞仪测定DC各亚型,分析IL-12和IFN-α表达水平与DC各亚型的相关性。结果①SLE组在第7天和第9天分泌的IL-12水平[(8.8±0.8)和(9.8±0.8)pg/ml]较对照组[(7.5±0.7)和(8.1±0.9)pg/ml]明显增加(P<0.05);SLE组第7天IFN-α水平[(4.0±0.8)pg/ml]较正常对照组[(2.9±0.8)pg/ml]水平升高显著(P<0.001)。②SLE组DC表达的CD1a、CD11c+、CD40、和CD123百分率(59±8、54±11、37±8、13±4)较对照组(48±4、43±9、29±7、10±4)明显增加(P<0.05),SLE患者DC表达的CD80和CD83(55±10、58±12)较对照组(48±12;48±9)升高不明显(P>0.05)。③分泌第7天和第9天的IL-12与CD1a、CD11c+、CD40保持良好的相关性(P<0.05),与CD80、CD83、CD123相关性不明显。第7天和第9天的IFN-α与CD1a、CD11c+、CD40、CD123存在明显相关性(P<0.05),而与CD80、CD83无相关性。

Objective To study the role of dendritic cells (DC) in systemic lupus erythematosus (SLE). The peripheral blood monocytes were induced to DC in SLE patients, the levels of interleukin (IL)-12 and interferon (IFN)-α secreted by DC were measured to analyze the correlation with DC subsets. Methods GM-CSF, IL-4 and TNF-α were used to induced matured DC, the expression of IL-12 and IFN-α in the cultivated supernatants were measured by ELISA. The immunofluorescence staining and flow cytometer were used to detect DC subsets, and the correlation between the IL-12 and IFN-α expression levels and DC subsets was analyzed. Results ① The IL-12 levels of SLE groups in the seventh and ninth day were [(8.8±0.8), (9.8±0.8) pg/ml] increased significantly than control groups [(7.5±0.7), (8.1±0.9) pg/ml] (P<0.05); the IFN-α level of SLE groups in the seventh day [(4.0±0.8) pg/ml] increased significantly than the normal control groups [(2.9±0.8) pg/ml] (P<0.001). ② The percentsage of CD1a, CD11c+, CD40 and CD123 expressed by DC in SLE groups (59±8, 54±11, 37±8, 13±4) were higher than control group (48±4, 43±9,29±7, 10±4) (P<0.05), but the percentsage of CD80 and CD83 (55±10, 58±11) in SLE groups and control groups (48±12, 48±9) had no significant differences (P>0.05). ③ The level of IL-12 had strong correlation with CD1a, CD11c+ and CD40 in the seventh and ninth days (P<0.05) but not with CD80, CD83 and CD123. The level of IFN-α had strong correlation with CD1a, CD11c+, CD40 and CD123 in the seventh and ninth days (P<0.05) but not with CD80 and CD83. Conclusion The levels of IL-12 and IFN-α secreted by induced DC are increased in SLE patients, and are correlated with DC subsets.They may play an important role in the development of SLE.