Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3–1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3–1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.

四溴邻苯二甲酸二(2-乙基己基)酯(TBPH)是一种新型溴化阻燃剂。一些研究表明，TBPH 暴露可能与甲状腺损伤有关。然而，关于动物或细胞中真实的暴露相关效应和分子机制的研究很少。在这项研究中，我们使用雄性 Sprague-Dawley (SD) 大鼠和 Nthy ori3-1 细胞系（人甲状腺滤泡上皮细胞）来探索 TBPH（5、50、500 mg/kg 和 1、10 mg/kg）的潜在影响。 ，100 nM）在甲状腺上。对细胞因子和甲状腺特异性蛋白、甲状腺球蛋白（TG）、甲状腺过氧化物酶（TPO）和碘化钠协同转运蛋白（NIS）的基因及其蛋白进行了检查，以研究可能的机制。实验结束时发现，50和500 mg/kg TBPH可显着提高总甲状腺素（TT4）和游离甲状腺素（FT4）水平。 500mg/kg剂量组大鼠甲状腺组织中Tg 、 Tpo 、白细胞介素6(Il6) 、白细胞介素10 ( Il10)信使RNA(mRNA)明显增强。同时，用 100 nM TBPH 处理的 Nthy ori3-1 细胞中TG 、 TPO 、 IL6和IL10的 mRNA 也升高。 IL6敲低后TG和TPO mRNA升高。令我们惊讶的是，在敲除IL10或抗IL-10受体（抗IL-10-R）抗体处理后， TG和TPO的mRNA显着减少，并且TBPH的影响减弱。总之，我们的结果表明 IL-10-IL-10R-TG/TPO-T4 轴是甲状腺中 TBPH 的重要靶点之一。