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
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Research Support, Non-U.S. Gov't
MeSH terms
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Annexin A5 / metabolism
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Antigens / immunology*
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Apoptosis / drug effects*
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Caspases / metabolism
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Cell Line
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DNA Fragmentation
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Enzyme Inhibitors / pharmacology*
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Fas Ligand Protein
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Humans
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Indoles / pharmacology*
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Maleimides / pharmacology*
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Membrane Glycoproteins / pharmacology
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / immunology
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Protein Kinase C / antagonists & inhibitors*
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Proto-Oncogene Proteins c-bcl-2 / analysis
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T-Lymphocytes / physiology*
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fas Receptor / physiology*
Substances
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Annexin A5
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Antigens
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Enzyme Inhibitors
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FASLG protein, human
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Fas Ligand Protein
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Indoles
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Maleimides
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Membrane Glycoproteins
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Proto-Oncogene Proteins c-bcl-2
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fas Receptor
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Protein Kinase C
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Caspases
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bisindolylmaleimide