综合分析揭示了BPS在人淋巴细胞上的免疫毒性机制
Integrated analysis reveals the immunotoxicity mechanism of BPs on human lymphocytes
影响因子:5.40000
分区:医学2区 / 毒理学1区 生化与分子生物学2区 药学2区
发表日期:2024 Aug 25
作者:
Qiujin Zhang, Mengzhen Li, Ping Wang, Xiao Lin, Keng Po Lai, Zhixiang Ding
摘要
双酚A（BPA）是一种有据可查的内分泌中断化学物质，广泛用于塑料产品中。除了其内分泌干扰作用外，BPA还表现出免疫毒性。许多国家由于对人类健康的不利影响而禁止BPA。近年来，已经使用了许多化学物质，例如Bisphenol B（BPB），Bisphenol E（BPE），Bisphenol S（BPS）和Bisphenol Fluorene（BHPF）替代BPA。由于这些替代化学物质具有类似于BPA的化学结构，因此它们也可能损害人类健康。但是，它们的免疫毒性和毒性基础的分子机制在很大程度上尚不清楚。这项研究的目的是通过将原发性人类淋巴细胞暴露于BPA及其替代化学物质来研究BPA及其替代化学物质的免疫毒性及其替代机制。我们的结果表明，暴露于BPA及其替代化学物质会改变白介素（IL）和细胞因子产生，例如IL-1B，IL-5，IL-6，IL-6，IL-8，Interferon alfa-2b（Ifn-A2b）和肿瘤坏死因子Alpha（TNF-α）（TNF-α），lymphocytees。其中，BPA和BHPF引起了更大的抑制作用。使用比较转录组分析，我们进一步研究了BHPF暴露改变的生物学过程和信号通路。我们的数据强调了通过放松基因簇的放松管制的人类淋巴细胞中免疫反应，T细胞功能和细胞因子受体相互作用的改变。此外，Ingenity途径分析的结果证明了T淋巴细胞功能的抑制，包括分化，运动和浸润。我们的结果首次描述了人类淋巴细胞中BHPF免疫毒性的基础机制。
Abstract
Bisphenol A (BPA) is a well-documented endocrine-disrupting chemical widely used in plastic products. In addition to its endocrine-disrupting effects, BPA exhibits immunotoxicity. Many countries have banned BPA because of its adverse effects on human health. In recent years, many chemicals such as bisphenol B (BPB), bisphenol E (BPE), bisphenol S (BPS), and bisphenol fluorene (BHPF) have been used to replace BPA. Because these replacement chemicals have chemical structures similar to that of BPA, they may also harm human health. However, their immunotoxicity and the molecular mechanisms underlying their toxicity remain largely unknown. The aim of this study was to investigate the immunotoxicity of BPA and its replacement chemicals, as well as the underlying mechanisms by exposing primary human lymphocytes to BPA and its replacement chemicals. Our results showed that exposure to BPA and its replacement chemicals altered the interleukin (IL) and cytokine production, such as IL-1b, IL-5, IL-6, IL-8, interferon alfa-2b (IFN-a2B), and tumor necrosis factor alpha (TNF-α), in the lymphocytes. Among these, BPA and BHPF caused a greater inhibition. Using comparative transcriptomic analysis, we further investigated the biological processes and signaling pathways altered by BHPF exposure. Our data highlighted alterations in the immune response, T cell function, and cytokine-cytokine receptor interactions in human lymphocytes through the deregulation of gene clusters. In addition, the results of ingenuity pathway analysis demonstrated the inhibition of T lymphocyte function, including differentiation, movement, and infiltration. Our results, for the first time, delineate the mechanisms underlying the immunotoxicity of BHPF in human lymphocytes.