Thymosin alpha1 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 immature developing thymocytes. Thymocyte apoptosis can be modulated by growth factors, anti-oxidants and adhesion receptors. We have previously demonstrated that thymosin alpha1 (Talpha1) antagonizes dexamethasone-induced apoptosis of CD4+CD8+ thymocytes. In the present study, we further characterize the dose and time dependence of Talpha1's antagonism of dexamethasone-induced thymocyte apoptosis. Talpha1 is effective at concentrations ranging from 2 to 100 microg/10(6) thymocytes. Talpha1 pre-treatment is necessary to achieve its anti-apoptotic activity. Talpha1 provides temporary protection to thymocytes by slowing dexamethasone's apoptotic activity up to 12 h post dexamethasone treatment. Additionally, Talpha1's activity is not sensitive to cycloheximide treatment, suggesting Talpha1's activity is independent of protein synthesis. Finally, Talpha1 is unable to antagonize apoptosis induced by the reactive oxygen species, H2O2, suggesting Talpha1'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 Talpha1 may provide a mechanism to transiently extend the life of a thymocyte during thymic selection.
Baumann
C A
CA
Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine and Health Sciences, 2300 Eye St. N.W., Washington, DC 20037, USA.
Badamchian
M
M
Goldstein
A L
AL
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D013947:Thymosin; D003907:Dexamethasone; D000077596:Thymalfasin