Partial synergy of bisindolylmaleimide with apoptotic stimulus in antigen-specific T cells--implications for multiple sclerosis.
In multiple sclerosis (MS), induction of T cell apoptosis constitutes a promising therapeutic strategy. Recently, bisindolylmaleimide has been shown to be an effective treatment of experimental autoimmune encephalomyelitis, presumably due to enhancement of CD95-mediated T cell apoptosis. Therefore, we studied the effects of bisindolylmaleimide on human (auto)antigen-specific T cells. We observed a synergistic effect of bisindolylmaleimide with apoptotic stimulus assessed via caspase activity and annexin V-binding, but no potentiation of DNA fragmentation or cell death. Thus, bisindolylmaleimide might be useful for modulating T cell apoptosis, yet more potent substances have to be generated re-establishing immunological control over auto-reactive T cells.
Wendling
U
U
Department of Neurology, University Hospital Charité, Schumannstr, Berlin, Germany.
Aktas
O
O
Schmierer
K
K
Zschenderlein
R
R
Zipp
F
F
D017304:Annexin A5 / Q000378:metabolism; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D053222:Fas Ligand Protein; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D017304:Annexin A5; D000941:Antigens; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007211:Indoles; D008301:Maleimides; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D011493:Protein Kinase C; D020169:Caspases; C088060:bisindolylmaleimide