Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats.

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Ecotoxicology and Environmental Safety Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI:10.1016/j.ecoenv.2024.117510
Baiming Jin, Yanbo Qi, Hong Chao, Xiaolei Yang, Hongjie Li, Siyuan Wan
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Abstract

Excessive iodine intake can induce autoimmune thyroiditis (AIT), and the methylation of programmed death receptor 2 (PD-L2) may be involved in the development of iodine-induced AIT. Here, we investigated the immune role of methylation of the susceptibility gene PD-L2 in the occurrence of iodine-induced AIT using the DNA methyltransferase inhibitor Decitabine (Dec) in an experimental autoimmune thyroiditis (EAT) rat model. After injecting Dec intraperitoneally into EAT rats, we performed arsenic-cerium catalytic spectrophotometry, pathological hematoxylin and eosin staining, enzyme-linked immunosorbent assay, quantitative methylation-specific polymerase chain reaction (qMSP), and quantitative real-time polymerase chain reaction (qPCR) to determine the relevant indices. The results showed that compared with the control group, the urinary iodine, thyroid lymphocyte infiltration, thyroglobulin antibody (TgAb), interferon (IFN-γ), and interleukin (IL-23) levels of the EAT rats were significantly increased. The PD-L2 methylation levels were significantly decreased in EAT rats compared to control rats, and the mRNA expression of the PD-L2 was significantly increased. Following Dec intervention, the methylation level of the PD-L2 in rats increased and interferon and interleukin-23 levels decreased, albeit not significantly. However, the mRNA expression of PD-L2 decreased significantly after Dec intervention, and the thyroid function of EAT rats also showed a gradual improvement trend. In summary, hypomethylation of PD-L2 is closely related to the development of iodine-induced AIT. Pro-inflammatory cellular factors are also involved in iodine-induced AIT progression. Although Dec shows promise in the treatment of AIT, further evaluation of its safety is necessary.

地西他滨对碘诱导自身免疫性甲状腺炎大鼠全血PD-L2甲基化的影响。
碘摄入过量可诱发自身免疫性甲状腺炎(AIT),程序性死亡受体2 (PD-L2)甲基化可能参与碘诱导的自身免疫性甲状腺炎(AIT)的发生。在此,我们在实验性自身免疫性甲状腺炎(EAT)大鼠模型中使用DNA甲基转移酶抑制剂地西他滨(Dec)研究了易感基因PD-L2甲基化在碘诱导AIT发生中的免疫作用。经腹腔注射Dec后,采用砷铈催化分光光度法、病理苏木精和伊红染色、酶联免疫吸附法、定量甲基化特异性聚合酶链反应(qMSP)、定量实时聚合酶链反应(qPCR)测定相关指标。结果显示,与对照组相比,进食大鼠尿碘、甲状腺淋巴细胞浸润、甲状腺球蛋白抗体(TgAb)、干扰素(IFN-γ)、白细胞介素(IL-23)水平均显著升高。与对照组相比,进食大鼠PD-L2甲基化水平显著降低,PD-L2 mRNA表达显著升高。经Dec干预后,大鼠PD-L2的甲基化水平升高,干扰素和白介素-23水平下降,但不明显。但经Dec干预后,PD-L2 mRNA表达明显下降,EAT大鼠甲状腺功能也呈现逐渐改善的趋势。综上所述,PD-L2的低甲基化与碘诱导AIT的发生密切相关。促炎细胞因子也参与碘诱导的AIT进展。虽然Dec在治疗AIT方面显示出前景,但对其安全性的进一步评估是必要的。
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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
期刊介绍: Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.
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