Ruggeri Rosaria M, Minuti Aurelio, Gianì Fiorenza, Masto Roberta, Romano Davide, Aliquò Federica, Campennì Alfredo, Campo Salvatore, Cannavò Salvatore, D'Ascola Angela
Department of Human Pathology of Adulthood and Childhood DETEV, Endocrine Unit, University of Messina, Messina, Italy.
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Endocrine. 2025 Jan;87(1):252-261. doi: 10.1007/s12020-024-04005-w. Epub 2024 Aug 23.
In this in vitro study, we investigated the effects of polychlorinated biphenyls (PCBs) on human thyrocytes, with a focus on the involvement of AhR, a key player in xenobiotic response, and the anti-oxidant Nrf-2/HO-1 pathway.
Primary cultured thyrocytes were exposed to the dioxin-like congeners PCB118 and PCB126 at 2.5 and 5 µM concentrations. mRNA expression was assessed by real-time PCR, and protein expression by Western Blot and ELISA, while protein quantification was assessed by densitometric analysis.
In cultured thyrocytes, PCB118 and PCB126 induced a significant (P < 0.01) increase of mRNA and protein levels of the pro-inflammatory cytokines IL-1beta and IL-6, while reducing those of thyroglobulin (TG) and NIS (p < 0.05), indicating down-regulation of these thyroid-specific genes in PCB-induced inflammation. ROS production also increased (p < 0.001). mRNA levels of AhR and the downstream molecules cytochrome P4501A, Nrf-2/HO-1 increased (p < 0.001), as well as related protein levels (p < 0.01), suggesting the activation of AhR and Nrf-2 pathways in response to PCBs exposure. AhR silencing decreased AhR-related gene expression and restored NIS and TG expression, while reducing inflammatory cytokines and oxidative stress markers (p < 0.05).
Dioxin-like PCBs (PCB118 and PCB126) may promote inflammation and oxidative stress in thyrocytes, impairing the expression of genes that are key players of thyroid function. These effects can be partially attributed to the activation of the AhR and Nrf-2 pathways. These data may contribute to explain the mechanisms underlying thyroid toxicity of PCBs, highlighting the potential role of these pollutants as a trigger of autoimmune thyroid inflammation and damage.
在本体外研究中，我们研究了多氯联苯（PCBs）对人甲状腺细胞的影响，重点关注外源性物质反应中的关键参与者芳烃受体（AhR）以及抗氧化剂核因子E2相关因子2/血红素加氧酶-1（Nrf-2/HO-1）途径的参与情况。
将原代培养的甲状腺细胞暴露于浓度为2.5和5μM的二噁英类同系物多氯联苯118（PCB118）和多氯联苯126（PCB126）中。通过实时聚合酶链反应（PCR）评估信使核糖核酸（mRNA）表达，通过蛋白质免疫印迹法（Western Blot）和酶联免疫吸附测定（ELISA）评估蛋白质表达，同时通过密度分析评估蛋白质定量。
在培养的甲状腺细胞中，PCB118和PCB126诱导促炎细胞因子白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的mRNA和蛋白质水平显著升高（P < 0.01），同时降低甲状腺球蛋白（TG）和钠碘同向转运体（NIS）的水平（P < 0.05），表明在PCB诱导的炎症中这些甲状腺特异性基因下调。活性氧（ROS）生成也增加（P < 0.001）。AhR以及下游分子细胞色素P4501A、Nrf-2/HO-1的mRNA水平升高（P < 0.001），相关蛋白质水平也升高（P < 0.01），表明在接触PCBs后AhR和Nrf-2途径被激活。AhR沉默降低了AhR相关基因表达，并恢复了NIS和TG表达，同时降低了炎症细胞因子和氧化应激标志物水平（P < 0.05）。
二噁英类PCBs（PCB118和PCB126）可能促进甲状腺细胞中的炎症和氧化应激，损害甲状腺功能关键基因的表达。这些影响可部分归因于AhR和Nrf-2途径的激活。这些数据可能有助于解释PCBs甲状腺毒性的潜在机制，突出这些污染物作为自身免疫性甲状腺炎症和损伤触发因素的潜在作用。
