机构地区:[1]首都医科大学附属北京安贞医院风湿免疫科,100029 [2]首都医科大学附属北京同仁医院检验科 [3]首都医科大学附属北京同仁医院风湿免疫科
出 处:《中国医药》2013年第7期995-997,共3页China Medicine
基 金:基金项目:首都医科大学基础-临床科研合作基金(10JL41、12JL16)
摘 要:目的探讨Th9细胞及相关细胞因子在类风湿关节炎(RA)中表达的改变及可能的机制。方法采集加例健康人(HC)和20例RA患者(RA组)的外周血,用酶联免疫吸附测定(ELISA)检测血清白细胞介素(IL)-9、IL_4、转化生长因子(TGF)-p和干扰素(IFN)-1水平;流式细胞术检测Th9细胞数;实时定量PCR检测IL-9mRNA、转录因子PU.1mRNA,分析这些指标可能的相互关系。结果RA组患者外周血中CIM+IL-9+T细胞、CIM+PU.1+T细胞、CIM+IL-9+PU.1+T细胞均缺如。细胞因子检测:IL-9水平在HC组为(1.24±0.44)×10^-9g/L,RA组为(1.334-0.53)×10^-9g/L(P=0.558);IL4水平在HC组为(8.59±4.07)×10^-9g/L,RA组为(5.95±5.73)×10^-9g/L(P=0.101);TGF—β水平在HC组为(12384-329)μg/L,RA组(712±254)μg/L,(P=0.00);IFN-γ水平在HC组均低于检测水平,RA患者中5例IFN-γ水平升高。HC组IL-9mRNA表达为(0.24±0.04),RA组为(0.24±0.02)(P=0.754);HC组PU.1mRNA表达为(0.38±0.02),RA组(0.13±0.02)(P=0.000)。结论RA组患者外周血促Th9分化关键细胞因子水平降低。抑制其分化关键细胞因子平有所升高,导致PU.1mRNA表达受抑,PU.1蛋白无法合成不能支持IL-9mRNA表达。RA患者外周血不存在Th9细胞分化条件,推测循环血‘n19细胞可能不参与RA发病机制。Objective To identify changes and possible functions of the T helper(Th) 9 cells in pathogene- sis of rheumatoid arthritis (RA). Methods Peripheral blood was taken from 20 RA patients and 20 healthy do- nors. Flow cytometry was used to analyze the subset of Th9 cells in peripheral blood from 5 RA patients. Interleukin (IL) -9, IL-4, transforming growth factor(TGF) -13 and interferon(IFN) -~/levels in sera of these subjects were test- ed by ELISA. The levels of IL-9 and PU. 1 mRNA expression were measured by reverse transcription( RT)-PCR. Results Percentage of CD4 + IL-9 + T cells was 0.09%. The serum levels of IL-9 did not increase in RA patients [ ( 1.33±0.53 ) x 10 -9 g/L ] than those of healthy controls [ ( 1.24±0.44) × 10 ^-9 g/L ] ( P 〉 0.05 ). CD4 + PU. 1 +T cells were 0.02%, CD4+ IL-9 + PU. 1 + T cells were not detectable in the peripheral blood of 5 RA pa- tients. The mRNA expression of IL-9 in CD4 + T cells in RA patients and healthy controls was (0.24 ± 0.02) and (0.24 ± 0.04) respectively(P 〉 0.05), but the expression of PU. 1 mRNA in CD4+T cells markedly decreased in RA patients (0.13 ± 0.025 ) than that of healthy controls (0.38 ± 0.025 ) ( P 〈 0.01 ). Serum levels of IL-4 in RA patients[ (5.95± 5.73) × 10^-9 g/L] did not increase than those of healthy controls[ (8.59 ±4.07) × 10^-9 g/L] ( P 〉 0.05 ). Meanwhile, levels of serum TGF-β significantly decreased in RA patients(712 ± 254) μg/L than those of healthy donors (1238 ± 329)μg/L(P 〈 0.01 ). IFN-γ levels were detectable in 5 patients with RA, while other samples for RA and healthy controls were not detectable. In short, low levels of IL-4 and TGF -13 could not support the expression of transcription factor PU. 1, which was the key factor for the differentiation of Th9 cells. So, this might identify why we could not find Th9 ceils in peripheral of RA patients. Conclusions In peripheral blood of RA patients, there is no T
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