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铅中毒影响接触铅工人外周血T淋巴细胞中与T细胞受体相关的基因表达模式。

Lead poisoning influences TCR-related gene expression patterns in peripheral blood T-lymphocytes of exposed workers.

作者信息

Niu Yuzhe, Yu Wei, Fang Su, Liu Sichu, Yang Zhiqian, Liu Weiwei, Chen Shaohua, Yang Lijian, Li Bo, Li Yangqiu

机构信息

Institute of Hematology, Medical College, Jinan University , Guangzhou , PR China .

出版信息

J Immunotoxicol. 2015 Jan-Mar;12(1):92-7. doi: 10.3109/1547691X.2014.899412. Epub 2014 Apr 10.

Abstract

Previous studies have shown that occupational lead (Pb) exposure might influence human T-lymphocyte function, including such as changes in T-cell receptor (TCR) Vβ and Vγ repertoire and in expression of the TCRζ gene. Thus, the study here further investigated expression of TCRζ-related factors and the FcεRIγ gene (whose product has a functional role complementary to the TCRζ chain) and the Elf-1 gene whose product is involved in regulation of TCR expression. Quantitative real-time RT-PCR was used to measure expression of TCRζ, FcεRIγ, and Elf-1 genes in peripheral blood mononuclear cells (PBMC) isolated from 17 Pb-exposed workers. Samples were collected before and after the workers had undergone chelation therapy regimens. Twenty-three healthy individuals served as controls. The results showed that TCRζ, FcεRIγ, and Elf-1 gene expression in Pb-exposed workers before chelation therapy was significantly lower than in PBMC from healthy individuals. After chelation therapy, expression of TCRζ appeared to trend toward normal levels; in comparison, lower expressions of FcεRIγ and Elf-1 persisted. In conclusion, the previously-documented impairment of T-lymphocyte functions and T- lymphocyte-mediated immune responses seen previously in response to occupational Pb exposure might be attributable, in part, to effects on TCR signaling pathways - including those related to TCRζ and FcεRIγ - and to any down-regulation of membrane TCRζ expression/activity that might be associated with Pb-induced effects on Elf-1 expression.

摘要

先前的研究表明,职业性铅(Pb)暴露可能会影响人类T淋巴细胞功能,包括T细胞受体(TCR)Vβ和Vγ库的变化以及TCRζ基因的表达变化。因此,本研究进一步调查了TCRζ相关因子、FcεRIγ基因(其产物具有与TCRζ链互补的功能作用)以及其产物参与TCR表达调控的Elf-1基因的表达。采用定量实时RT-PCR检测从17名铅暴露工人分离的外周血单个核细胞(PBMC)中TCRζ、FcεRIγ和Elf-1基因的表达。在工人接受螯合治疗方案前后采集样本。23名健康个体作为对照。结果显示,螯合治疗前铅暴露工人的TCRζ、FcεRIγ和Elf-1基因表达显著低于健康个体的PBMC。螯合治疗后,TCRζ的表达似乎趋向于正常水平;相比之下,FcεRIγ和Elf-1的表达持续较低。总之,先前记录的职业性铅暴露导致的T淋巴细胞功能和T淋巴细胞介导的免疫反应受损,可能部分归因于对TCR信号通路的影响——包括与TCRζ和FcεRIγ相关的通路——以及可能与铅诱导的对Elf-1表达的影响相关的膜TCRζ表达/活性的任何下调。

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