Expression of c-FLIPL and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide

F Willems, Z Amraoui, N Vanderheyde, V. Verhasselt, E Aksoy, C Scaffidi, ME Peter, PH Krammer, M Goldman

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Abstract

To gain insight into the mechanisms controlling apoptosis of dendritic cells (DC), human monocyte-derived DC were analyzed for their expression of CD95 (Fas/Apo-1) and their response to CD95 ligation, Although DC expressed the CD95 molecule on their membrane, they did not undergo apoptosis on CD95 ligation unless sensitized by cycloheximide. In parallel, DC synthesized c-FLIPL, an inhibitor of the CD95-mediated death-signaling cascade. We also demonstrated that bisindolylmaleimide down-regulates c-FLIPL expression in DC and, in parallel, allows CD95-mediated apoptosis in these cells. In contrast, Bcl-2, Bcl-x(L),, and Bax levels were not affected by bisindolylmaleimide. We conclude that DC resist CD95-mediated apoptosis in association with c-FLIPL expression and that the immunosuppressive potential of bisindolylmaleimide previously observed at the T-cell level also involves facilitation of CD95-mediated DC apoptosis. (Blood, 2000;95: 3478-3482) (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)3478-3482
Number of pages5
JournalBlood
Volume95
Issue number11
Publication statusPublished - 1 Jun 2000

Cite this

Willems, F., Amraoui, Z., Vanderheyde, N., Verhasselt, V., Aksoy, E., Scaffidi, C., Peter, ME., Krammer, PH., & Goldman, M. (2000). Expression of c-FLIPL and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide. Blood, 95(11), 3478-3482.