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

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-indu...

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Main Authors: Baiming Jin, Yanbo Qi, Hong Chao, Xiaolei Yang, Hongjie Li, Siyuan Wan
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324015860
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author Baiming Jin
Yanbo Qi
Hong Chao
Xiaolei Yang
Hongjie Li
Siyuan Wan
author_facet Baiming Jin
Yanbo Qi
Hong Chao
Xiaolei Yang
Hongjie Li
Siyuan Wan
author_sort Baiming Jin
collection DOAJ
description 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.
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spelling doaj-art-d6ebab5b400047e6ad86b7fa144c1e4b2025-01-23T05:25:49ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117510Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis ratsBaiming Jin0Yanbo Qi1Hong Chao2Xiaolei Yang3Hongjie Li4Siyuan Wan5Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaDepartment of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaDepartment of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaDepartment of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaDepartment of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaCorresponding author.; Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaExcessive 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.http://www.sciencedirect.com/science/article/pii/S0147651324015860iodineautoimmune thyroiditisEAT ratPD-L2methylationdecitabine
spellingShingle Baiming Jin
Yanbo Qi
Hong Chao
Xiaolei Yang
Hongjie Li
Siyuan Wan
Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
Ecotoxicology and Environmental Safety
iodine
autoimmune thyroiditis
EAT rat
PD-L2
methylation
decitabine
title Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
title_full Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
title_fullStr Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
title_full_unstemmed Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
title_short Effect of decitabine on PD-L2 methylation in whole blood of iodine-induced autoimmune thyroiditis rats
title_sort effect of decitabine on pd l2 methylation in whole blood of iodine induced autoimmune thyroiditis rats
topic iodine
autoimmune thyroiditis
EAT rat
PD-L2
methylation
decitabine
url http://www.sciencedirect.com/science/article/pii/S0147651324015860
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