Decreased expressions of the TNF-alpha signaling adapters in peripheral blood mononuclear cells (PBMCs) are correlated with disease activity in patients with systemic lupus erythematosus
Decreased expressions of the TNF-alpha signaling adapters in peripheral blood mononuclear cells (PBMCs) are correlated with disease activity in patients with systemic lupus erythematosus
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外周血单核细胞 (PBMC) 中 TNF-α 信号转导接头表达的降低与系统性红斑狼疮患者的疾病活动度相关
DOI：
10.1007/s10067-006-0531-8
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Yu, Xueqing
中科院分区：
文献类型：
--
作者：
Zhu, Langjing;Yang, Xiao;Yu, Xueqing
肿瘤坏死因子（TNF）-α是一种多效性细胞因子。系统性红斑狼疮（SLE）是一种自身免疫性炎症性疾病。然而，到目前为止，TNF适配体在SLE中的表达和病理生理作用还知之甚少。本研究的目的是研究肿瘤坏死因子受体相关死亡结构域（TRADD）蛋白、Fas相关死亡结构域（FADD）蛋白、受体相互作用蛋白1（RIP-1）、和外周血单核细胞（PBMC）中的TNF受体相关因子-2（TRAF-2）探讨这些接头蛋白的表达与SLE疾病活动性的关系。从51名SLE患者和17名健康受试者的静脉血中分离PBMC。通过半定量逆转录聚合酶链反应（RT-PCR）和定量实时RT-PCR分析PBMC中TNF衔接分子（如TRADD、FADD、RIP-1和TRAF-2）的mRNA表达。TRADD、FADD、RIP-1和TRAF-2的mRNA在健康受试者的PBMC中存在组成性表达。SLE患者PBMCs中各衔接分子mRNA的表达均显著降低，分别为对照组的0.38、0.69、0.59和0.55倍（P< 0.05）。Caspase 3在SLE患者中的表达明显增高（P< 0.01），而IL-1 β在SLE患者和正常对照组中的表达无明显差异。SLE患者PBMC中TRADD、FADD、RIP-1和TRAF-2的表达与SLEDAI呈负相关，相关系数分别为-0.285、-0.280、-0.307和-0.298（P< 0.05）。SLE患者外周血单个核细胞中TNF接头分子TRADD、FADD、RIP-1和TRAF-2的mRNA表达显著降低，且这些接头分子的表达与SLE活动指数呈负相关。这些异常可能参与了SLE中由异常的TNF-α信号通路介导的免疫病理损伤。
Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine. Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease. However, until now, the expression and pathophysiological role of TNF adapters in SLE have been poorly understood. This study aims to investigate the expression of mRNA for the TNF adapter proteins including TNF receptor-associated death domain (TRADD) protein, Fas-associated death domain (FADD) protein, receptor-interacting protein 1 (RIP-1), and TNF receptor-associated factor-2 (TRAF-2) in peripheral blood mononuclear cells (PBMCs) from patients with SLE and to explore the relationship between the expression of these adapters and the SLE disease activity. PBMCs were isolated from the venous blood of 51 SLE patients and 17 healthy subjects. The expression of mRNA for TNF adapter molecules such as TRADD, FADD, RIP-1, and TRAF-2 in PBMCs were analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT–PCR) and quantitative real-time RT–PCR. There were constitutive expressions of mRNA for TRADD, FADD, RIP-1, and TRAF-2 in PBMCs from healthy subjects. The expression of mRNA for all the adapter molecules significantly decreased in PBMCs from patients with SLE, which were 0.38-, 0.69-, 0.59-, and 0.55-fold, respectively, compared to those of control subjects (P< 0.05). The expression of Caspase 3 was significantly increased in SLE patients (P< 0.01); however, the expression of IL-1beta was not significantly different between SLE and control subjects. The expression of TRADD, FADD, RIP-1, and TRAF-2 in PBMCs from patients with SLE were negatively correlated with SLEDAI, the correlation coefficient of which was −0.285, −0.280, −0.307, and −0.298, respectively (P< 0.05). The expression of mRNA for TNF adapter molecules TRADD, FADD, RIP-1, and TRAF-2 decreased significantly in PBMCs from patients with SLE, and the expression of these adapters were negatively correlated with the SLE activity index. These abnormalities may be involved in the immunopathogenic injury mediated by the aberration TNF-alpha signaling pathway in SLE.