Thymosin α1 is a time and dose-dependent antagonist of dexamethasone-induced apoptosis of murine thymocytes in vitro

Thymosin α1 is a time and dose-dependent antagonist of dexamethasone-induced apoptosis of murine thymocytes in vitro
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DOI:
10.1016/s0192-0561(00)00065-5
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发表时间:
2000-12-01
期刊:
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子:
--
通讯作者:
Goldstein, AL
Goldstein, AL
中科院分区:
其他
文献类型:
--
作者:
Baumann, CA;Badamchian, M;Goldstein, AL

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It is well established that glucocorticoid hormones induce apoptosis in immature developing thymocytes. Thymocyte apoptotsis can be modulated by growth factors, anti-oxidants and adhesion receptors. We have previously demonstrated that thymosin alpha (1) (T alpha (1)) antagonizes dexamethasone-induced apoptosis of CD4(+)CD8(+) thymocytes. In the present study, we further characterize the dose and time dependence of T alpha (1)'s antagonism of dexamethasone-induced thymocyte apoptosis. Ta, is effective at concentrations ranging from 2 to 100 mug/10(6) thymocytes. T alpha (1),s pre-treatment is necessary to achieve its anti-apoptotic activity. Tee, provides temporary protection to thymocytes by slowing dexamethasone's apoptotic activity up to 12 h post dexamethasone treatment. Additionally, T alpha (1)'s activity is not sensitive to cycloheximide treatment, suggesting T alpha (1)'s activity is independent of protein synthesis. Finally, Tee, is unable to antagonize apoptosis induced by the reactive oxygen species, H2O2. suggesting T alpha (1)'s antagonism of dexamethasone occurs at the early stages of dexamethasone-induced apoptosis, prior to the production of reactive oxygen species. This evidence suggests that Ta, may provide a mechanism to transiently extend the life of a thymocyte during thymic selection. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.