Polychlorinated Biphenyls (PCBS)-induced oxidative stress and inflammation in human thyrocytes: involvement of AhR and NRF-2/HO-1 pathway.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2025-01-01 Epub Date: 2024-08-23 DOI:10.1007/s12020-024-04005-w

Rosaria M Ruggeri, Aurelio Minuti, Fiorenza Gianì, Roberta Masto, Davide Romano, Federica Aliquò, Alfredo Campennì, Salvatore Campo, Salvatore Cannavò, Angela D'Ascola

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Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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多氯联苯（PCBS）诱导的人类甲状腺细胞氧化应激和炎症：AhR和NRF-2/HO-1途径的参与

目的：在这项体外研究中，我们调查了多氯联苯（PCBs）对人类甲状腺细胞的影响，重点研究了异生物反应中的关键角色 AhR 和抗氧化剂 Nrf-2/HO-1 通路的参与情况：方法：将原代培养的甲状腺细胞暴露于浓度分别为 2.5 µM 和 5 µM 的二恶英类同源物 PCB118 和 PCB126：结果：在培养的甲状腺细胞中，PCB118 和 PCB126 会诱导甲状腺细胞发生显著的（P二恶英类多氯联苯（PCB118 和 PCB126）可能会促进甲状腺细胞的炎症和氧化应激，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 通路的激活。这些数据可能有助于解释多氯联苯的甲状腺毒性机制，突出了这些污染物作为自身免疫性甲状腺炎症和损伤的触发因素的潜在作用。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.