Overexpression of the anti-apoptotic oncogene, bcl-2, in the thymus does not prevent thymic atrophy induced by estradiol or 2,3,7, 8-tetrachlorodibenzo-p-dioxin.
Overexpression of the anti-apoptotic oncogene, bcl-2, in the thymus does not prevent thymic atrophy induced by estradiol or 2,3,7, 8-tetrachlorodibenzo-p-dioxin.
复制标题
胸腺中抗凋亡癌基因 bcl-2 的过度表达并不能阻止雌二醇或 2,3,7,8-四氯二苯并-对二恶英诱导的胸腺萎缩。
DOI：
10.1006/taap.1998.8446
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发表时间：
1998
影响因子：
3.8
通讯作者：
Silverstone,AE
中科院分区：
文献类型：
--
作者：
Staples,JE;Fiore,NC;FrazierJr,DE;Gasiewicz,TA;Silverstone,AE
地塞米松（Dex）、雌二醇（E2）和2，3，7，8-四氯二苯并二恶英（TCDD）都会影响免疫系统，导致免疫抑制和胸腺萎缩。目前还不确定这些化合物如何以及在何处引起胸腺萎缩。然而，已经表明这些化合物可能具有相似的作用和靶点，即，Dex和TCDD诱导未成熟胸腺细胞凋亡，Dex和E2优先靶向双阳性细胞。Thelckpr-bcl-2转基因小鼠已被证明对Dex诱导的胸腺萎缩具有保护作用。我们用这种小鼠模型来确定bcl-2表达是否也能保护E2和TCDD诱导的胸腺萎缩。我们的研究结果表明，虽然bcl-2转基因（TG+）小鼠是完全保护由单剂量的地塞米松诱导的萎缩，萎缩仍然诱导这些小鼠与E2或TCDD治疗。TG−和TG+小鼠胸腺细胞的表型分析也显示了Dex、E2和TCDD诱导的萎缩的不同结果。最后，由于存在不依赖于bcl-2的凋亡替代途径，因此使用TUNEL测定直接检查TG−和TG+胸腺细胞的凋亡迹象。在TCDD和E2处理后，即使在早期时间点和高剂量水平下，TG−或TG+小鼠也没有可检测到的凋亡迹象。这些结果表明，有不同的机制Dex，E2和TCDD在胸腺中的作用，细胞凋亡不是E2和TCDD诱导的胸腺萎缩的关键机制。
Dexamethasone (Dex), estradiol (E2), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) all affect the immune system, causing immunosuppression and thymic atrophy. It is still uncertain how and where these compounds act to induce thymic atrophy. However, it has been suggested that these compounds may have similar actions and targets, i.e., apoptosis of immature thymocytes for Dex and TCDD and preferential targeting of double-positive cells by Dex and E2. Thelckpr-bcl-2 transgenic mouse has been shown to be protected against Dex-induced thymic atrophy. We used this murine model to determine if bcl-2 expression would also protect against E2- and TCDD-induced thymic atrophy. Our results indicate that, although the bcl-2 transgenic (TG+) mice were fully protected from atrophy induced by a single dose of Dex, atrophy was still induced in these mice following treatment with E2 or TCDD. Phenotypic analysis of thymocytes from TG− and TG+ mice also showed distinct consequences of atrophy induced by Dex, E2, and TCDD. Finally, since there are alternative pathways for apoptosis that are bcl-2 independent, both TG− and TG+ thymocytes were examined directly for indications of apoptosis using the TUNEL assay. After TCDD and E2 treatment there were no detectable signs of apoptosis in either TG− or TG+ mice even at early time points and at elevated dose levels. These results indicate that there are distinct mechanisms for the actions of Dex, E2, and TCDD in the thymus and that apoptosis is not a key mechanism of E2- and TCDD-induced thymic atrophy.