Thymosin alpha(1) is a time and dose-dependent antagonist of dexamethasone-induced apoptosis of murine thymocytes in vitro

It is well established that glucocorticoid hormones induce apoptosis in imm ature developing thymocytes. Thymocyte apoptotsis can be modulated by growt h factors, anti-oxidants and adhesion receptors. We have previously demonst rated that thymosin alpha (1) (T alpha (1)) antagonizes dexamethasone-induc ed apoptosis of CD4(+)CD8(+) thymocytes. In the present study, we further c haracterize the dose and time dependence of T alpha (1)'s antagonism of dex amethasone-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 p rotection 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 activit y is independent of protein synthesis. Finally, Tee, is unable to antagoniz e apoptosis induced by the reactive oxygen species, H2O2. suggesting T alph a (1)'s antagonism of dexamethasone occurs at the early stages of dexametha sone-induced apoptosis, prior to the production of reactive oxygen species. This evidence suggests that Ta, may provide a mechanism to transiently ext end the life of a thymocyte during thymic selection. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rig hts reserved.