Cyclosporin A is a metabolite of the fungi Trichoderma polysporum, Cyclosporin A (CsA) is a cyclic polypeptide consisting of 9 amino-acids to inhibit nitric oxide synthesis induced by interleukin 1alpha, lipopolysaccharides and TNFα. CsA is an immunosuppressant. Studies in animals indicate that cyclosporin inhibits the development of cell-mediated reactions, including allograft immunity, delayed cutaneous hypersensitivity, experimental allergic encephalomyelitis, Freund's adjuvant arthritis, graft-versus-host disease and also T-cell dependent antibody production. Also inhibits lymphokine production and release and appears to block resting lymphocytes in the G0 or G1 phase of the cell cycle. CsA binds to cyclophilin and inhibits the T-cell receptor signal transduction pathway via the formation of cyclpsporin A-cyclophilin complex. The CsA-cyclophilin complex inhibits PP2 (calcineurin, a type 2B phosphatase). Calcineurin inhibition interferes with other physiological processes as well. It inhibits mitochondrial permeability transition pore opening. However, pore inhibition becomes less efficient at increasing Ca2+ loads and inhibition is transient. Inhibits staurosporin-induced apoptosis in cultured neural cells and rotenone-induced apoptosis in PC-12 cells.
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