β-Cypermethrin and its metabolite 3-phenoxybenzoic acid induce cytotoxicity and block granulocytic cell differentiation in HL-60 cells
β-Cypermethrin and its metabolite 3-phenoxybenzoic acid induce cytotoxicity and block granulocytic cell differentiation in HL-60 cells
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DOI：
10.1093/abbs/gmy068
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发表时间：
2018-08-01
影响因子：
3.7
通讯作者：
Fu, Zhengwei
中科院分区：
文献类型：
--
作者：
He, Bingnan;Wang, Xia;Fu, Zhengwei
使用最广泛的II型拟除虫菊酯是高效氯氰菊酯(β-CYP)，3-苯氧基苯甲酸(3-PBA)是其主要代谢产物之一。尽管CYP对某些免疫细胞具有毒性作用，但到目前为止，CYP对免疫祖细胞的免疫毒性作用还没有得到很好的研究。在本研究中，我们评价了β-CYP和3-PBA对人早幼粒白血病细胞株HL-60的免疫毒性。β-CYP和3-PBA都降低了细胞存活率。此外，β-CYP和3-PBA均以剂量和时间依赖的方式刺激固有的细胞凋亡途径，而只有β-CYP诱导细胞周期停滞于G1期。此外，暴露于100mU M的β-CYP和3-PBA可抑制全反式维甲酸(ATRA)诱导的粒细胞分化相关基因CD11b和CSF-3R的mRNA表达。此外，暴露于β-CYP和3-PBA导致粒细胞分化促进转录因子PU的下调。1和C/EBP epsilon。此外，我们还发现，β-CYP和3-PBA暴露可导致细胞内活性氧(ROS)水平升高，N-乙酰半胱氨酸(NAC)可阻断其毒性作用。本研究结果为β-CYP和3-PBA对早幼粒细胞的免疫毒性作用及其可能的机制提供了证据。
The most widely used type II pyrethroid is beta-cypermethrin (beta-CYP), and 3-phenoxybenzoic acid (3-PBA) is one of its primary metabolites. Although CYP has been shown to pose toxic effects in some immune cells, as of now the immunotoxicity of CYP on immune progenitor cells has not been well studied. In this study, we evaluated the immunotoxicity of beta-CYP and 3-PBA on the human promyelocytic leukemia cell line, HL-60. Both beta-CYP and 3-PBA reduced cell viability. In addition, both beta-CYP and 3-PBA stimulated the intrinsic apoptotic pathway in a dose- and time-dependent manner, while only beta-CYP induced cell cycle arrest in G1 stage. Moreover, exposure to beta-CYP and 3-PBA at 100 mu M inhibited all-trans retinoic acid (ATRA)-induced mRNA expressions of the granulocytic differentiation-related genes, CD11b and CSF-3R. Furthermore, exposure to beta-CYP and 3-PBA resulted in a downregulation of the granulocytic differentiation promoting transcriptional factors, PU. 1 and C/EBP epsilon. Furthermore, we found that beta-CYP and 3-PBA exposure led to elevated levels of cellular reactive oxygen species (ROS), and that pretreatment with N-acetylcysteine (NAC) blocked the toxic effects caused by beta-CYP and 3-PBA. The results obtained in the present study provide evidence showing the immunotoxic effects of beta-CYP and 3-PBA on promyelocytic cells as well as its possible underlying mechanism.