Bisindolylmaleimide VIII facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases

Fas-mediated apoptosis is essential for the elimination of cells, and impaired apoptosis can have severe detrimental consequences. Bisindolyimaleimide VIII potentiated Pas-mediated apoptosis in human astrocytoma 1321N1 cells and in Molt-4 T cells, both of which were devoid of apoptosis induced by anti-fas antibody in the absence of bisindolylmaleimide VIII, and in Jurkat and CEM-B T cells, which showed slight and moderate apoptotic responses, respectively, to low levels of Fas stimulation. Potentiation of Fas-mediated apoptosis by bisindolylmaleimide VIII was elective for activated, rather than non-activated, T cells, and was Pas-dependent, as it was not observed in T cells from Fas-deficient lpr/lpr mice. Administration of bisindolylmaleimide VIII to rats during autoantigen stimulation prevented the development of symptoms of T cell-mediated autoimmune diseases in two models, the Lewis rat model of experimental allergic encephalitis and the Lewis adjuvant arthritis model. Thus, the use of agents such as bisindolylmaleimide VIII may be therapeutically useful for supporting more effective elimination of detrimental cells through enhancement of Pas-dependent apoptosis signaling.