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Effects of endocrine active contaminating pesticides on RACK1 expression and immunological consequences in THP-1 cells
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2022-09-06 , DOI: 10.1016/j.etap.2022.103971
Ambra Maddalon 1 , Mirco Masi 2 , Martina Iulini 1 , Pasquale Linciano 3 , Valentina Galbiati 1 , Marina Marinovich 1 , Marco Racchi 3 , Erica Buoso 4 , Emanuela Corsini 1
Affiliation  

We have previously demonstrated that RACK1, which expression is under steroid hormone control, plays an important role in the activation of immune cells and its expression can be useful to evaluate the immunotoxic profile of endocrine disrupting chemicals (EDCs). Hence, we investigated the effects of three contaminating and persistent pesticides: the fungicide vinclozolin (VIN), the herbicide atrazine (ATR) and the insecticide cypermethrin (CYP) on RACK1 expression and on innate immune response. VIN resulted in modest alteration of RACK1 while ATR and CYP reduced in a dose dependent manner RACK1 expression, ultimately leading to the decrease in lipopolysaccharide‐induced IL‐8 and TNF-α release and CD86 and CD54 surface marker expression. Moreover, our data indicate that, after exposure to EDCs, alterations of RACK1 expression can also occur with mechanisms not directly mediated by an interaction with a nuclear or membrane steroid receptors. Therefore, RACK1 could represent a useful EDCs screening tool to evaluate their immunotoxic potential and to dissect their mechanisms of action.



中文翻译:

内分泌活性污染农药对 THP-1 细胞 RACK1 表达和免疫学后果的影响

我们之前已经证明,在类固醇激素控制下表达的 RACK1 在免疫细胞的激活中起重要作用,其表达可用于评估内分泌干扰化学品 (EDC) 的免疫毒性特征。因此,我们研究了三种污染性和持久性农药对 RACK1 表达和先天免疫反应的影响:杀菌剂长春唑啉 (VIN)、除草剂阿特拉津 (ATR) 和杀虫剂氯氰菊酯 (CYP)。VIN 导致 RACK1 的适度改变,而 ATR 和 CYP 以剂量依赖性方式降低 RACK1 表达,最终导致脂多糖诱导的 IL-8 和 TNF-α 释放以及 CD86 和 CD54 表面标志物表达减少。此外,我们的数据表明,在接触 EDC 后,RACK1 表达的改变也可能发生在不直接由与核或膜类固醇受体相互作用介导的机制下。因此,RACK1 可以代表一种有用的 EDC 筛选工具,以评估其免疫毒性潜力并剖析其作用机制。

更新日期:2022-09-06
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