TNF-α信号通路主要受体衔接蛋白在SLE患者外周血单个核细胞中的表达及其意义

Expression of tumor necrosis factor-α signaling adapter proteins in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

目的探讨肿瘤坏死因子(TNF)α信号通路主要受体衔接蛋白-肿瘤坏死因子相关死亡结构域蛋白(TRADD)、Fas 相关死亡结构域蛋白(FADD)、受体相互作用蛋白1(RIP-1)和肿瘤坏死因子受体相关因子2(TRAF-2)在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的表达变化及意义。方法收集本院确诊的 SLE 住院患者(51例)和健康志愿者(17例)外周静脉血,分离PBMC,采用实时荧光定量 PCR 检测上述4种受体衔接蛋白及半胱氨酸蛋白水解酶(Caspase)3和白细胞介素(IL)-1β的表达水平,比较 SLE 患者与健康志愿者之间以及不同狼疮活动度 SLE 患者中上述4种受体衔接蛋白的表达差异,以及与狼疮活动指数之间的相关关系。结果正常对照组PBMC中可表达 TRADD、FADD、RIP-1和 TRAF-2。SLE 患者 PBMC 中 TRADD、FADD、RIP-1和 TRAF-2表达分别为止常对照组的0.38,0.69,0.59和0.55倍(P<0.05);SLE 高活动度组4种受体衔接蛋白的表达分别为正常对照组的0.31,0.59,0.52和0.49倍(P<0.05),但低活动度组与正常对照组之间的差异无统计学意义(P>0.05)。SLE 患者 PBMC 中 Caspase 3表达明显升高(P<0.01),而 IL-1β表达与正常对照组之间差异无统计学意义(P>0.05)。SLE 患者 PBMC 中 TRADD、FADD、RIP-1和TRAF-2的表达与狼疮活动指数(SLEDAI)均呈负相关关系,相关系数分别为-0.285,-0.280,-0.307和-0.298(P<0.05)。结论 TNF-α信号通路中主要的4种受体衔接蛋白 TRADD、FADD、RIP-1和 TRAF-2在 SLE 患者 PBMC 中的表达均降低,且与狼疮活动指数呈负相关关系,其异常表达可能参与了 TNF-α信号网络紊乱所介导的 SLE 免疫病理损伤。

Objective To investigate the mRNA expression of the tumor necrosis factor （TNF） - adapter proteins, TNF receptor-associated death domain protein （TRADD）, Fas-associated death domain protein （ FADD）, receptor-interacting protein 1 （ RIP-1 ） , and TNF receptor-associated factor-2 （ TRAF-2 ） in peripheral blood mononuclear cells （PBMC） from patients with systemic lupus erythematosus （SLE）, and to explore the relationship between the expression of these adaptors and the SLE disease activity. Methods PBMC were isolated from venous blood of 51 SLE patients and 17 healthy subjects. The mRNA expression of TRADD, FADD, RIP-1, TRAF-2, Caspase 3, and interleukin （IL）-1β were analyzed by quantitative real time RT-PCR. Disease activity was measured using the SLE Disease Activity Index （SLEDAI）. Results All healthy subjects showed mRNA expressions of TRADD, FADD, RIP-1, and TRAF-2. The mRNA expression levels of TRADD, FADD, RIP-1, and TRAF- in the PBMC from the patients were 0.38, 0.69, 0.59, and 0.55 tomes that from the control subjects （ all P 〈 0.05 ）. The expression levels of these 4 adapters of the SLE patients with the SLEDAI ≥ 10 were significantly lower than those of the SLE patients with the SLEDAI 〈 10 （ all P 〈 0.05 ）. The Caspase3 mRNA expression of the SLE patients was significantly higher than that of the healthy controls （P 〈 0.01 ）; however, the IL-1β mRNA expression was not significantly different between the SLE and control subjects. The mRNA expression levels of TRADD, FADD, RIP-1 and TRAF-2 in the PBMC from the SLE patients were all negatively correlated with the SLE activity index with the coefficient correlation of - 0. 285, - 0. 280, - 0. 307, and - 0. 298 respectively （all P 〈 0.05 ）. Conclusion The mRNA expression levels of the TNF adapter molecules, such as TRADD, FADD, RIP-1, and TRAF-2, decrease significantly in the PBMC from the SLE patients, and are negatively correlated with the SLE activity index. These abnormalities may participate in the immunopathogenic injury mediated by the aberration TNFα signaling pathway in SLE.