Niu Yuzhe, Yu Wei, Fang Su, Liu Sichu, Yang Zhiqian, Liu Weiwei, Chen Shaohua, Yang Lijian, Li Bo, Li Yangqiu
Institute of Hematology, Medical College, Jinan University , Guangzhou , PR China .
J Immunotoxicol. 2015 Jan-Mar;12(1):92-7. doi: 10.3109/1547691X.2014.899412. Epub 2014 Apr 10.
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.
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。