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

Abstract

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 α₁ (Tα₁) antagonizes dexamethasone-induced apoptosis of CD4⁺CD8⁺ thymocytes. In the present study, we further characterize the dose and time dependence of Tα₁'s antagonism of dexamethasone-induced thymocyte apoptosis. Tα₁ is effective at concentrations ranging from 2 to 100 μg/10⁶ thymocytes. Tα₁ pre-treatment is necessary to achieve its anti-apoptotic activity. Tα₁ provides temporary protection to thymocytes by slowing dexamethasone's apoptotic activity up to 12 h post dexamethasone treatment. Additionally, Tα₁'s activity is not sensitive to cycloheximide treatment, suggesting Tα₁'s activity is independent of protein synthesis. Finally, Tα₁ is unable to antagonize apoptosis induced by the reactive oxygen species, H₂O₂, suggesting Tα₁'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 Tα₁ may provide a mechanism to transiently extend the life of a thymocyte during thymic selection.