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TRAIL and DR5 Promote Thyroid Follicular Cell Apoptosis in Iodine Excess-Induced Experimental Autoimmune Thyroiditis in NOD Mice

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Abstract

Death receptor-mediated apoptosis has been implicated in target organ destruction in patients with chronic autoimmune thyroiditis. Several apoptosis signaling pathways, such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), have been shown to be active in thyroid cells and may be involved in destructive thyroiditis. Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet, but its pathogenic role remains unclear. The effects of excessive iodine on TRAIL and its death receptor expression in thyroid were investigated. Experimental autoimmune thyroiditis (EAT) was induced by excessive iodine and thyroglobulin (Tg) in non-obese diabetic mice. The expression of TRAIL and its death receptor DR5 was detected by immunofluorescence staining. Following administration of excessive iodine alone, Tg, and excessive iodine combined with Tg, TRAIL-positive cells appear not only in follicular cells but also in lymphocytes infiltrated in the thyroid, whereas DR5-positive cells appear only in follicular cells. Large numbers of CD3-positive cells and a few CD22-positive cells were detected in thyroid. A great amount of follicular cells were labeled specifically by terminal deoxynucleotide transferase-mediated deoxynucleotide triphosphate nick-end labeling assay. Taken together, our results suggest that excessive iodine could induce TRAIL and DR5 abnormal expression in thyroid. TRAIL band with DR5 to promote follicular cells apoptosis thus mediate thyroid destruction in EAT.

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Acknowledgments

This work was supported by the Science and Technology Council of Tianjin (grant no. 05YFGDSF02700) for scientific research. The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

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  1. Key Lab of Hormone and Institute of Endocrinology, Metabolic Disease Hospital, Tianjin Medical University of Tianjin, 127#, Tianjin Medical University of Tianjin, 300070, Tianjin, China

    Xiujie Yu, Lanying Li, Qingxin Li, Xiaoyi Zang & Zebing Liu

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  1. Xiujie Yu
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  2. Lanying Li
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Correspondence to Lanying Li.

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Yu, X., Li, L., Li, Q. et al. TRAIL and DR5 Promote Thyroid Follicular Cell Apoptosis in Iodine Excess-Induced Experimental Autoimmune Thyroiditis in NOD Mice. Biol Trace Elem Res 143, 1064–1076 (2011). https://doi.org/10.1007/s12011-010-8941-5

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