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

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.

• Authors: U Wendling, O Aktas, K Schmierer, R Zschenderlein, F Zipp
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 103 Issue 1 Pg. 69-75 (Feb 01 2000) ISSN: 0165-5728 [Print] Netherlands
• PMID: 10674991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, immunology)
• Protein Kinase C (antagonists & inhibitors)
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• T-Lymphocytes (physiology)
• fas Receptor (physiology)