Cao Lanqin, Wei Lai, Du Qiaoyun, Su Ying, Ye Shuzi, Liu Kaihua
Xiangya Hospital, Central South University, Changsha 410078, China.
Xiangya School of Public Health, Central South University, Changsha 410078, China.
Toxics. 2023 Feb 27;11(3):231. doi: 10.3390/toxics11030231.
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphorus flame retardant that has been utilized in recent years as a primary replacement for polybrominated diphenyl ethers (PBDEs) in a wide variety of fire-sensitive applications. However, the impact of TDCPP on the immune system has not been fully determined. As the largest secondary immune organ in the body, the spleen is considered to be an important study endpoint for determining immune defects in the body. The aim of this study is to investigate the effect of TDCPP toxicity on the spleen and its possible molecular mechanisms. In this study, for 28 consecutive days, TDCPP was administered intragastrically (i.g), and we assessed the general condition of mice by evaluating their 24 h water and food intake. Pathological changes in spleen tissues were also evaluated at the end of the 28-day exposure. To measure the TDCPP-induced inflammatory response in the spleen and its consequences, the expression of the critical players in the NF-κB pathway and mitochondrial apoptosis were detected. Lastly, RNA-seq was performed to identify the crucial signaling pathways of TDCPP-induced splenic injury. The results showed that TDCPP intragastric exposure triggered an inflammatory response in the spleen, likely through activating the NF-κB/IFN-γ/TNF-α/IL-1β pathway. TDCPP also led to mitochondrial-related apoptosis in the spleen. Further RNA-seq analysis suggested that the TDCPP-mediated immunosuppressive effect is associated with the inhibition of chemokines and the expression of their receptor genes in the cytokine-cytokine receptor interaction pathway, including four genes of the CC subfamily, four genes of the CXC subfamily, and one gene of the C subfamily. Taken together, the present study identifies the sub-chronic splenic toxicity of TDCPP and provides insights on the potential mechanisms of TDCPP-induced splenic injury and immune suppression.
磷酸三（1,3 - 二氯 - 2 - 丙基）酯（TDCPP）是一种有机磷阻燃剂，近年来在各种对火灾敏感的应用中被用作多溴二苯醚（PBDEs）的主要替代品。然而，TDCPP对免疫系统的影响尚未完全确定。作为体内最大的次级免疫器官，脾脏被认为是确定体内免疫缺陷的重要研究终点。本研究的目的是探讨TDCPP毒性对脾脏的影响及其可能的分子机制。在本研究中，连续28天经胃内（i.g.）给予TDCPP，通过评估小鼠24小时的水和食物摄入量来评估其一般状况。在28天暴露期结束时，还评估了脾脏组织的病理变化。为了测量TDCPP诱导的脾脏炎症反应及其后果，检测了NF - κB途径和线粒体凋亡中的关键因子的表达。最后，进行RNA测序以鉴定TDCPP诱导的脾脏损伤的关键信号通路。结果表明，经胃内暴露TDCPP引发了脾脏的炎症反应，可能是通过激活NF - κB/IFN - γ/TNF - α/IL - 1β途径。TDCPP还导致了脾脏中线粒体相关的凋亡。进一步的RNA测序分析表明，TDCPP介导的免疫抑制作用与细胞因子 - 细胞因子受体相互作用途径中趋化因子及其受体基因表达的抑制有关，包括CC亚家族的四个基因、CXC亚家族的四个基因和C亚家族的一个基因。综上所述，本研究确定了TDCPP的亚慢性脾脏毒性，并提供了关于TDCPP诱导脾脏损伤和免疫抑制潜在机制的见解。
