摘要
二噁英是芳烃受体(aryl hydrocarbon receptor,AHR)的高效外源配体,已知可以通过AHR发挥免疫毒性作用。经典的AHR毒性通路是指AHR由配体激活后进入细胞核,并与芳烃受体核转运蛋白(AHR nuclear translocator,ARNT)形成复合物,诱导二噁英反应元件(dioxin response element,DRE)控制的下游免疫相关基因的表达。但新的研究表明二噁英诱导免疫毒性还存在多种非经典的AHR通路,即激活后的AHR与其他信号通路(如炎症反应、细胞周期和信号转导)中的关键蛋白之间发生相互串扰,影响细胞功能。该过程中,AHR直接或以AHR-ARNT复合物的形式与其他转录因子相互作用,协同募集到共识或非共识DRE位点并与之结合,进而影响关键分子的转录和表达。目前已有许多与二噁英结构相似的物质被证明具有类二噁英的AHR激活活性,包括部分多氯联苯、多环芳烃和多溴联苯醚等,被称为类二噁英物质(dioxin-like compounds,DLCs)。DLCs可以通过激活AHR影响免疫系统,但一些研究表明,部分DLCs的免疫毒性可通过非AHR依赖的途径产生,这些途径可能包括导致细胞氧化应激、影响细胞呼吸爆发反应、促进细胞凋亡和干扰线粒体功能等。总之,与二噁英相比,DLCs的免疫毒性作用机制并不清晰,还需要更为系统的研究。
Dioxins are highly potent exogenous ligands of aryl hydrocarbon receptor(AHR),which are known to exert immunotoxic effects through AHR.The canonical AHR toxicity pathway is that activated AHR enters the nucleus and forms a complex with AHR nuclear translocator(ARNT),inducing the expression of downstream immune-related genes controlled by dioxin response element(DRE).However,new studies have shown that non-canonical AHR pathways are responsible to dioxin-induced immunotoxicity to some extent.Non-canonical AHR pathways refer to that activated AHR cross-talk with key proteins in other signaling pathways(such as inflammation,cell cycle,signal transduction),affecting cell function.In this process,AHR directly or in the form of AhRARNT complex interacts with other transcription factors,and they are collaboratively recruited and bind to consensus or non-consensus DRE sites,then affecting the transcription and expression of key molecules.At present,many substances with similar structure to dioxins have been proved to have dioxin-like AHR activation activity,including some polychlorinated biphenyls(PCBs),polycyclic aromatic hydrocarbons(PAHs),polybrominated diphenyl ethers(PBDEs),which are called dioxin-like compounds(DLCs).DLCs can affect the immune system by activating AHR,but AHR-independent pathways have been also suggested in some research,which could include causing cells to oxidative stress,affecting respiratory burst response,interfering with mitochondrial function and promoting cell apoptosis,etc.In conclusion,compared with dioxins,the immunotoxic mechanism of DLCs is not clear,and more systematic studies are needed.
作者
王鑫格
李娜
韩颖楠
马梅
吴兴华
李翀
王殿常
Wang Xinge;Li Na;Han Yingnan;Ma Mei;Wu Xinghua;Li Chong;Wang Dianchang(CAS Key Laboratory of Drinking Water Science and Technology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China;State Key Laboratory of Environmental Aquatic Chemistry,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China;National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery,Beijing 100085,China;University of Chinese Academy of Sciences,Beijing 100049,China;China Three Gorges Corporation,Beijing 100038,China)
出处
《生态毒理学报》
CAS
CSCD
北大核心
2023年第1期138-148,共11页
Asian Journal of Ecotoxicology
基金
国家重点研发计划课题(2021YFC3200803)
中国长江三峡集团有限公司科研项目(201903139)
场地土壤环境基准推导及表征关键技术(2019YFC1804604)。
关键词
二噁英
类二噁英物质
芳烃受体
免疫毒性
dioxins
dioxin-like compounds
aryl hydrocarbon receptor
immunotoxicity
