College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
Environ Toxicol. 2019 Jun;34(6):742-752. doi: 10.1002/tox.22740. Epub 2019 Mar 5.
Brominated flame retardants (BFRs) are supposed to act as disruptors of cell signaling, but the underlying mechanisms remain less clear. Human bronchial epithelial cells (BEAS-2B) were used to investigate the toxic effect and gene expression changes induced by tetrabromobisphenol A (TBBPA). By genome-wide approaches with Illumina RNA-seq, 87 genes were identified to exhibit ≥1.5-fold changes in expression after treatment by TBBPA for 48 h, among which, 79 were upregulated and 8 were downregulated. Gene ontology (GO) annotation enriched unigenes were divided into three clusters: biological process (BP), cellular component (CC) and molecular function (MF). Pathway analysis showed that NF-κB, TNF signaling, toll-like receptor, MAPK signaling and B-cell receptor were the most prominent pathways affected by TBBPA, which play key roles in regulating cell proliferation and cell differentiation, inflammatory response. Finally, for verifying the accuracy of microarray analysis, qRT-PCR was used to analyze the transcription level of key genes in the above signaling pathways, and ELISA assay confirmed the effect of TBBPA on the levels of CXCL-2, CCL-3, CCL-4, IL-1β, TNF-α, and IL-6. These findings provided important information for further exploitation of the mechanisms under-lying BFR-induced adverse health effects.
溴系阻燃剂（BFRs）被认为是细胞信号转导的干扰物，但潜在的机制仍不太清楚。本研究采用人支气管上皮细胞（BEAS-2B），探讨四溴双酚 A（TBBPA）引起的毒性作用和基因表达变化。通过 Illumina RNA-seq 的全基因组方法，鉴定出 87 个基因在 TBBPA 处理 48 小时后表达水平发生了≥1.5 倍的变化，其中 79 个基因上调，8 个基因下调。GO 注释富集的基因被分为三个簇：生物过程（BP）、细胞成分（CC）和分子功能（MF）。通路分析表明，NF-κB、TNF 信号、Toll 样受体、MAPK 信号和 B 细胞受体是受 TBBPA 影响最显著的通路，这些通路在调节细胞增殖和细胞分化、炎症反应中发挥关键作用。最后，为了验证微阵列分析的准确性，采用 qRT-PCR 分析了上述信号通路中关键基因的转录水平，ELISA 测定证实了 TBBPA 对 CXCL-2、CCL-3、CCL-4、IL-1β、TNF-α和 IL-6 水平的影响。这些发现为进一步探讨 BFR 引起的不良健康影响的机制提供了重要信息。
