T cell selective apoptosis by a novel immunosuppressant, FTY720, is closely regulated with Bcl‐2
Y Nagahara, M Ikekita… - British journal of …, 2002 - Wiley Online Library
Y Nagahara, M Ikekita, T Shinomiya
British journal of pharmacology, 2002•Wiley Online LibraryA novel immunosuppressant FTY720 caused a significant decrease in peripheral T
lymphocytes, but not in B lymphocytes upon oral administration. This decrease was mainly a
result of FTY720‐induced apoptosis. In this study, we confirmed FTY720‐induced T cell
selective apoptosis using lymphoma cell lines in vitro. Viability loss, DNA fragmentation,
Annexin V binding, and caspases activation (caspase‐3,‐8, and‐9) were observed in Jurkat
cells (T lymphoma cells), but not significantly in BALL‐1 cells (B lymphoma cells). These …
lymphocytes, but not in B lymphocytes upon oral administration. This decrease was mainly a
result of FTY720‐induced apoptosis. In this study, we confirmed FTY720‐induced T cell
selective apoptosis using lymphoma cell lines in vitro. Viability loss, DNA fragmentation,
Annexin V binding, and caspases activation (caspase‐3,‐8, and‐9) were observed in Jurkat
cells (T lymphoma cells), but not significantly in BALL‐1 cells (B lymphoma cells). These …
- A novel immunosuppressant FTY720 caused a significant decrease in peripheral T lymphocytes, but not in B lymphocytes upon oral administration. This decrease was mainly a result of FTY720‐induced apoptosis. In this study, we confirmed FTY720‐induced T cell selective apoptosis using lymphoma cell lines in vitro.
- Viability loss, DNA fragmentation, Annexin V binding, and caspases activation (caspase‐3, ‐8, and ‐9) were observed in Jurkat cells (T lymphoma cells), but not significantly in BALL‐1 cells (B lymphoma cells). These results indicated that FTY720 selectively induced apoptosis in T cell lymphoma to a greater extent than in B cell lymphoma, a finding that is similar to the result observed when FTY720 was treated with T lymphocytes and B lymphocytes in vitro.
- FTY720 released cytochrome c from mitochondria in Jurkat intact cells as well as from isolated Jurkat mitochondria directly, but not from mitochondria in BALL‐1 cells nor from isolated BALL‐1 mitochondria.
- BALL‐1 cells and B cells had more abundant mitochondria‐localized anti‐apoptotic protein Bcl‐2 than did Jurkat cells and T cells.
- FTY720‐induced apoptosis is inhibited by the overexpression of Bcl‐2, suggesting that the cellular Bcl‐2 level regulates the sensitivity to FTY720.
British Journal of Pharmacology (2002) 137, 953–962. doi:10.1038/sj.bjp.0704970
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