| First Author | Delfino DV | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 13 | Pages | 4134-41 |
| PubMed ID | 15319285 | Mgi Jnum | J:95270 |
| Mgi Id | MGI:3525767 | Doi | 10.1182/blood-2004-03-0920 |
| Citation | Delfino DV, et al. (2004) Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice. Blood 104(13):4134-41 |
| abstractText | Glucocorticoids promote thymocyte apoptosis and modulate transcription of numerous genes. GILZ (glucocorticoid-induced leucine zipper), being one of them, is strongly up-regulated in the thymus. To elucidate its function we generated transgenic mice overexpressing it specifically in the T-cell lineage and characterized its influence on thymus function. In young adult transgenic mice CD4(+)CD8(+) thymocyte number was significantly decreased and ex vivo thymocyte apoptosis was increased. Apoptotic pathway analysis detected reduced antiapoptotic B-cell leukemia XL (Bcl-xL) expression and increased activation of caspase-8 and caspase-3. Time-course experiments showed that in wild-type (WT) thymocytes GILZ up-regulation was followed by sequential Bcl-xL decreased expression and activation of caspase-8 and of caspase-3. Moreover, GILZ delivered inside WT thymocytes by a fusion protein with the transactivator of transcription (TAT) peptide decreased Bcl-xL and promoted their apoptosis. In aged mice perturbation of thymic subset numbers was amplified over time, as demonstrated by a further decrease in CD4(+)CD8(+) cells and increases in CD4(+)CD8(-), CD4(-)CD8(-), and CD8(+)CD4(-) cell counts. These results support the hypothesis that GILZ participates in the regulation of thymocyte apoptosis by glucocorticoids. |
