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

To gain insight into the mechanisms controlling apoptosis of dendritic cell s (DC), human monocyte-derived DC were analyzed for their expression of CD9 5 (Fas/Apo-1) and their response to CD95 ligation, Although DC expressed th e CD95 molecule on their membrane, they did not undergo apoptosis on CD95 l igation unless sensitized by cycloheximide. In parallel, DC synthesized c-F LIPL, an inhibitor of the CD95-mediated death-signaling cascade. We also de monstrated that bisindolylmaleimide down-regulates c-FLIPL expression in DC and, in parallel, allows CD95-mediated apoptosis in these cells. In contra st, Bcl-2, Bcl-x(L),, and Bax levels were not affected by bisindolylmaleimi de. We conclude that DC resist CD95-mediated apoptosis in association with c-FLIPL expression and that the immunosuppressive potential of bisindolylma leimide 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.