Dexamethasone, beta-estradiol, and 2,3,7,8-tetrachlorodibenzo-p-dioxin elicit thymic atrophy through different cellular targets.
Dexamethasone, beta-estradiol, and 2,3,7,8-tetrachlorodibenzo-p-dioxin elicit thymic atrophy through different cellular targets.
复制标题
地塞米松、β-雌二醇和 2,3,7,8-四氯二苯并-对二恶英通过不同的细胞靶点引起胸腺萎缩。
DOI：
10.1006/taap.1994.1114
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发表时间：
1994
影响因子：
3.8
通讯作者：
Gasiewicz,TA
中科院分区：
文献类型：
--
作者：
Silverstone,AE;FrazierJr,DE;Fiore,NC;Soults,JA;Gasiewicz,TA
本文观察了地塞米松（DEX）、β-雌二醇-17-戊酸酯（E_2）和2，3，7，8-四氯二苯并二恶英（TCDD）对胸腺萎缩动力学及相关骨髓和胸腺细胞表型改变的影响。这些结果意味着这些化合物的作用机制存在差异。在三种化合物中，DEX在3天内诱导最大萎缩，在第12天完全恢复。在最大萎缩点，RAG-1+TdT+ CD 4 +8+ 3胸腺细胞群比例最大。相反，TCDD和E2在第12天引起最大胸腺萎缩。E2处理，如DEX，导致RAG-1+TdT+ CD 4 +8+ 3 int群体的优先减少，但与DEX不同，这种减少持续存在。TCDD诱导的胸腺萎缩是由于所有类型的胸腺细胞的比例损失。TCDD对胸腺中TdT+RAG-1+细胞无明显的相对减少作用。TCDD和E2对骨髓中TdT和RAG-1的缓慢和持续减少与DEX治疗动物骨髓中这些标记物的快速减少和快速恢复形成对比。另外的研究表明，只有DEX诱导的萎缩伴随着胸腺细胞凋亡的诱导，如在前24小时内通过多个核小体长度DNA片段检测到的。萎缩胸腺中亚群的不同动力学和比例，以及RAG和TdT表达改变的不同模式，以及细胞凋亡的存在或不存在为这些药物引起胸腺萎缩的不同机制提供了证据。E2和TCDD诱导的胸腺萎缩的缓慢诱导和较长的持续时间，以及它们对骨髓干细胞标志物的影响，表明骨髓胸腺细胞前体是这些药物的主要靶点。
The effects of single doses of dexamethasone (DEX), β-estradiol-17-valerate (E2), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the kinetics of thymic atrophy and related bone marrow and thymocyte phenotqpe alterations were examined. The results imply differences in the mechanisms by which these compounds act. Of the three compounds, DEX induced maximal atrophy by 3 days with complete recovery by Day 12. At the point of maximal atrophy, the RAG-1+TdT+CD4+8+3intthymocyte population was proportionately the most depleted. In contrast, TCDD and E2 caused maximal thymic atrophy by Day 12. E2 treatment, like DEX, resulted in a preferential decrease in the RAG-1+TdT+CD4+8+3intpopulation, but unlike DEX, this decrease persisted. TCDD-induced thymic atrophy resulted from a proportional loss of all classes of thymocytes. There was no significant relative reduction of TdT+RAG-1+cells by TCDD in the thymus. A slow and persistent reduction of TdT and RAG-1 in bone marrow by both TCDD and E2 contrasted with the rapid reduction and quick recovery of these markers in marrow from DEX-treated animals. Additional studies showed that only DEX-induced atrophy was accompanied by the induction of thymocyte apoptosis, as detected by multiple nucleosomal length DNA fragments within the first 24 hr. The different kinetics and proportions of subsets in the atrophied thymuses, as well as the distinct patterns of alterations of RAG and TdT expression, and the presence or the absence of apoptosis provide evidence for different mechanisms of thymic atrophy by these agents. The slow induction and longer persistence of thymic atrophy induced by E2 and TCDD, as well as their effects on bone marrow stem cell markers, suggest that bone marrow thymocyte precursors are major targets for these agents.