Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
Dipartimento di Scienze del Farmaco, Università Degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia, Italy; Scuola Universitaria Superiore IUSS, Piazza della Vittoria 15, 27100 Pavia, Italy.
Environ Toxicol Pharmacol. 2022 Oct;95:103971. doi: 10.1016/j.etap.2022.103971. Epub 2022 Sep 6.
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.
我们之前已经证明,受类固醇激素控制的表达的 RACK1 在免疫细胞的激活中发挥重要作用,其表达可用于评估内分泌干扰化学物质(EDCs)的免疫毒性特征。因此,我们研究了三种污染和持久性农药:杀真菌剂咯菌腈(VIN)、除草剂莠去津(ATR)和杀虫剂氯菊酯(CYP)对 RACK1 表达和先天免疫反应的影响。VIN 导致 RACK1 略有改变,而 ATR 和 CYP 则以剂量依赖的方式降低 RACK1 的表达,最终导致脂多糖诱导的 IL-8 和 TNF-α释放以及 CD86 和 CD54 表面标记物表达减少。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,其机制不是直接通过与核或膜甾体受体相互作用介导的。因此,RACK1 可以作为一种有用的 EDCs 筛选工具,用于评估其免疫毒性潜力,并剖析其作用机制。