Partial synergy of bisindolylmaleimide with apoptotic stimulus in antigen-specific T cells--implications for multiple sclerosis

J Neuroimmunol. 2000 Feb 1;103(1):69-75. doi: 10.1016/s0165-5728(99)00214-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Antigens / immunology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line
  • DNA Fragmentation
  • Enzyme Inhibitors / pharmacology*
  • Fas Ligand Protein
  • Humans
  • Indoles / pharmacology*
  • Maleimides / pharmacology*
  • Membrane Glycoproteins / pharmacology
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Protein Kinase C / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • T-Lymphocytes / physiology*
  • fas Receptor / physiology*

Substances

  • Annexin A5
  • Antigens
  • Enzyme Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Indoles
  • Maleimides
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Protein Kinase C
  • Caspases
  • bisindolylmaleimide