Abstract
Apoptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. The death receptor CD95 (APO-1/Fas) and its ligand (L) CD95L are critically involved in activation-induced-cell-death (AICD) of activated T-cells. Here we show that the anti-inflammatory sesquiterpene lactone parthenolide derived from the European traditional herb-medicine feverfew and many Mexican India medicinal plants suppresses expression of the CD95L and CD95 at the mRNA levels, thus, preventing T-cells from AICD. We demonstrate that parthenolide blocks NF-κB binding to the two NF-κ binding sites of the CD95L promoter and suppresses promoter activity upon T-cell activation. Aberrant expression of CD95 and, particularly CD95L is dangerous and may lead to severe diseases. Our study indicates that parthenolide supports T-cell survival by down-regulating the CD95 system, at least in part, and, therefore, may have therapeutic potential as a new anti-apoptotic substance against AICD in T-cells.
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Abbreviations
- TCR:
-
T-cell receptor
- AICD:
-
activation-induced-cell-death
- SL:
-
sesquiterpene lactone
- PMA:
-
phorbol 12-myristate 13-acetate
- RT–PCR:
-
reverse transcription-polymerase chain reaction
- EMSA:
-
electrophoretic mobility shift assay
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Acknowledgements
We thank S Parg and WW Müller for technical help, Drs A Israel and ML Schmitz for providing IκBα and IκBβ expression plasmids and the pluc-Bax plasmid.
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Li-Weber, M., Giaisi, M., Baumann, S. et al. The anti-inflammatory sesquiterpene lactone parthenolide suppresses CD95-mediated activation-induced-cell-death in T-cells. Cell Death Differ 9, 1256–1265 (2002). https://doi.org/10.1038/sj.cdd.4401102
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DOI: https://doi.org/10.1038/sj.cdd.4401102
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