Advanced oxidation protein products induce apoptosis in thyroid follicular epithelial cells through oxidative stress in Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder primarily driven by T cell. The apoptosis of the follicular thyroid cells plays an important role in HT apart from the lymphocyte-mediated cytotoxicity. Advanced oxidation protein products (AOPPs), resulting from oxidative stress, are known to be involved in various inflammatory diseases. However, their role in HT development has not been explored. Here, we discovered that AOPP levels were significantly elevated in thyroid tissues of both HT patients (Ctrl 4.12 ± 0.56, HT 30.00 ± 2.78; p < 0.0001) and experimental autoimmune thyroiditis (EAT) mice (Ctrl 8.37 ± 1.43, HT 55.82 ± 2.87; p < 0.0001), accompanied by extensive thyroid follicular epithelial cell apoptosis in HT patients (Ctrl 32.16 ± 1.79, HT 147.10 ± 13.32; p < 0.0001) and EAT mice (Ctrl 66.78 ± 6.72, HT 249.10 ± 9.77; p < 0.0001). In vitro study showed that AOPPs induced reactive oxygen species (ROS) production via nicotinamide adenine dinucleotide phosphate oxidase (NOX), leading to apoptosis in human thyroid follicular epithelial cell (Nthy-ori 3-1). Treatment with apocynin, a NOX inhibitor, reduced AOPP-induced ROS production and apoptosis in Nthy-ori 3-1 cells, and in turn alleviated thyroid follicular epithelial cell apoptosis and autoimmune thyroiditis symptoms in mice. Mechanistically, AOPP treatment activated JNK pathway, leading to the downregulation of Bcl-2, upregulation of Bax, the mitochondrial membrane potential depolarization and consequently triggered the activation of mitochondria-dependent intrinsic apoptosis pathway. Collectively, our findings highlight the promotive roles of AOPP in HT and provide an attractive therapeutic target for HT therapy. Copyright © 2025 Elsevier B.V. All rights reserved.

Citation

Jie Tan, Ruoting Ding, Shitong Yu, Kewu Tu, Jixiang Zheng, Jiayuan Zou, Junna Ge, Zhigang Wei, Tingting Li, Zhicheng Zhang, Weisheng Chen, Shangtong Lei, Baihui Sun. Advanced oxidation protein products induce apoptosis in thyroid follicular epithelial cells through oxidative stress in Hashimoto's thyroiditis. International immunopharmacology. 2025 Feb 20;148:114069

Mesh Tags

Substances

PMID: 39826455

search → result