Mori K, Mori M, Stone S, Braverman L E, DeVito W J
Division of Endocrinology, University of Massachusetts Medical Center, Worcester 01655, USA.
Eur J Endocrinol. 1998 Nov;139(5):539-45. doi: 10.1530/eje.0.1390539.
Several lines of evidence suggest that tumor necrosis factor-alpha (TNFalpha) may contribute to the pathogenesis of autoimmune thyroid disease. It is not known, however, whether increased thyroidal TNFalpha levels are associated with changes in thyroid function. The purpose of the present study was to utilize in situ hybridization histochemistry and immunohistochemistry to determine if the expression of TNF-alpha in the thyroid is associated with a decrease in thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA levels. Lymphocytic thyroiditis was induced in BB/Wor rats by iodide administration, and thyroidal Tg and TPO mRNA levels were assessed by Northern blot analysis and in situ hybridization, and TNFalpha expression by Northern blot analysis and immunohistochemistry. Thyroids were obtained before and 1 and 2 months after iodide administration. Hematoxylin and eosin staining revealed that there was a progressive increase in mononuclear cells in the thyroids of BB/Wor rats ingesting iodide for 1 and 2 months. Northern blot analysis revealed that during the same time course there was a progressive increase in TNFalpha mRNA levels and a progressive decrease in Tg and TPO mRNA levels in the thyroids. In situ hybridization histochemistry was performed to determine if the decrease in Tg and TPO mRNA levels was associated with thyroid follicular cells in contact with infiltrating mononuclear cells. In rats treated with iodide for 1 month, there was a modest decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. After 2 months of iodide treatment there was clearly a localized decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. Immunohistochemical analysis did not detect TNFalpha in the thyroids from control rats or from rats treated with iodide for 1 month. In contrast, after 2 months of treatment, TNFalpha was easily detected in infiltrating mononuclear cells and in some thyroid follicular cells. Together, these results suggest that the suppression of Tg and TPO mRNA levels was associated with the expression of TNFalpha and thus are in agreement with in vitro studies demonstrating that TNFalpha inhibits thyroid cell function.
多项证据表明，肿瘤坏死因子-α（TNFα）可能在自身免疫性甲状腺疾病的发病机制中起作用。然而，尚不清楚甲状腺中TNFα水平升高是否与甲状腺功能变化有关。本研究的目的是利用原位杂交组织化学和免疫组织化学来确定甲状腺中TNF-α的表达是否与甲状腺球蛋白（Tg）和甲状腺过氧化物酶（TPO）mRNA水平的降低有关。通过给BB/Wor大鼠喂食碘化物诱导淋巴细胞性甲状腺炎，并用Northern印迹分析和原位杂交评估甲状腺Tg和TPO mRNA水平，用Northern印迹分析和免疫组织化学评估TNFα表达。在喂食碘化物之前以及之后1个月和2个月获取甲状腺。苏木精和伊红染色显示，摄入碘化物1个月和2个月的BB/Wor大鼠甲状腺中的单核细胞逐渐增多。Northern印迹分析显示，在同一时间进程中，甲状腺中TNFα mRNA水平逐渐升高，而Tg和TPO mRNA水平逐渐降低。进行原位杂交组织化学以确定Tg和TPO mRNA水平的降低是否与接触浸润单核细胞的甲状腺滤泡细胞有关。在喂食碘化物1个月的大鼠中，接触浸润单核细胞的滤泡细胞中Tg和TPO mRNA水平有适度降低。碘化物治疗2个月后，接触浸润单核细胞的滤泡细胞中Tg和TPO mRNA水平明显出现局部降低。免疫组织化学分析未在对照大鼠或喂食碘化物1个月的大鼠的甲状腺中检测到TNFα。相比之下，治疗2个月后，在浸润的单核细胞和一些甲状腺滤泡细胞中很容易检测到TNFα。这些结果共同表明，Tg和TPO mRNA水平的抑制与TNFα的表达有关，因此与体外研究结果一致，即TNFα抑制甲状腺细胞功能。
