| RRC ID |
1422
|
| 著者 |
Yamauchi R, Morita A, Yasuda Y, Grether-Beck S, Klotz LO, Tsuji T, Krutmann J.
|
| タイトル |
Different susceptibility of malignant versus nonmalignant human T cells toward ultraviolet A-1 radiation-induced apoptosis.
|
| ジャーナル |
J Invest Dermatol
|
| Abstract |
Ultraviolet (UV) A-1 (340-400 nm) radiation is highly effective in inducing apoptosis in skin-infiltrating T cells and thereby exerts beneficial effects in patients with T cell-mediated skin diseases. In this in vitro study, we report that malignant and normal T cells differ in their susceptibility toward UVA-1 radiation-induced apoptosis. Dose-response studies revealed that malignant CD4+ T cells isolated from a patient with adult T cell leukemia and Sezary's syndrome as well as malignant T cell lines exhibited a significantly higher susceptibility toward UVA-1 radiation-induced apoptosis 4 h (early apoptosis) and 24 h (late apoptosis) after exposure than normal, CD4+ T cells. This difference was specific for UVA-1 irradiation because it was not detected when apoptosis was induced in these cells through exposure to UVB radiation or stimulation with cell-permeable ceramides. It has been shown that UVA-1 radiation-induced T cell apoptosis is initiated through the generation of singlet oxygen. This is in agreement with the present observation that stimulation of unirradiated cells with a singlet oxygen-generating system induced apoptosis in malignant cells to a greater extent than in normal cells. Moreover, downregulation of FAS surface expression in malignant T cells was associated with the inhibition of UVA-1 radiation/singlet oxygen-induced apoptosis in these cells. It was thus of great interest to learn that addition of the caspase inhibitor Z-VADfmk decreased and interferon-gamma stimulation, which is known to upregulate caspase levels including caspase-3, increased the sensitivity of T cells toward UVA-1 radiation-induced apoptosis. Furthermore, malignant T cells had significantly higher procaspase-3 levels when compared with normal cells. These studies indicate that the susceptibility of human T cells toward UVA-1 radiation-induced apoptosis is related to the availability of caspases such as caspase-3 and that strategies directed at upregulating caspase levels will increase the efficacy of UVA-1 phototherapy.
|
| 巻・号 |
122(2)
|
| ページ |
477-83
|
| 公開日 |
2004-2-1
|
| DOI |
10.1046/j.0022-202X.2003.22106.x
|
| PII |
S0022-202X(15)30656-4
|
| PMID |
15009733
|
| MeSH |
Apoptosis / radiation effects*
Caspase 3
Caspases / metabolism
Cell Line, Tumor
Humans
Leukemia, T-Cell*
T-Lymphocytes / cytology*
T-Lymphocytes / enzymology
T-Lymphocytes / radiation effects*
Ultraviolet Rays
|
| IF |
7.143
|
| 引用数 |
18
|
|
WOS 分野
|
DERMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Jurkat(RCB0806)
MOLT-4(RCB0206) |
