Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis.
Transcriptional expression of a gene or genes is absolutely required for induction of glucocorticoid-induced thymocyte apoptosis. We have previously shown that expression of T cell death-associated gene 8 (TDAG8) is quickly induced exclusively in the thymus after dexamethasone (DEX) treatment. Here, we present data that TDAG8 expression is induced prior to induction of DEX-mediated apoptosis. In contrast, TDAG8 expression in thymocytes was not induced in the process of gamma-irradiation-mediated apoptosis. TDAG8 expression accelerated only DEX-induced, but not TCR-mediated or gamma-irradiation-induced, thymocyte apoptosis in transgenic mice overexpressing TDAG8. Interestingly, these effects were specifically detected in CD4(+)CD8(+) double-positive thymocytes. Moreover, activation of caspase-3, -8 and -9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation. In conclusion, TDAG8 expression is involved in glucocorticoid-induced signals to activate caspase-9, -8 and -3 for subsequent apoptosis induction in CD4(+)CD8(+) double-positive thymocytes.
Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. tosa@imm.hokudai.ac.jp
Noriko
N
Tosa
Masaaki
M
Murakami
Wen Yi
WY
Jia
Minesuke
M
Yokoyama
Taro
T
Masunaga
Chikako
C
Iwabuchi
Manabu
M
Inobe
Kazuya
K
Iwabuchi
Tadaaki
T
Miyazaki
Kazunori
K
Onoe
Makoto
M
Iwata
Toshimitsu
T
Uede
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D015152:Blotting, Northern; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005938:Glucocorticoids / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
C513337:GPR65 protein, mouse; D005938:Glucocorticoids; D043562:Receptors, G-Protein-Coupled; D020169:Caspases