A, ciclosporin, cyclosporine, cyclosporin is an
immunosuppressant reagent which is used to lower the activity of T
cells and their immune response.
Cyclosporin A binds to the cytosolic protein cyclophilin (immunophilin)
of lymphocytes, especially T cells. This complex of ciclosporin and
cyclophilin inhibits calcineurin, which, under normal circumstances,
is responsible for activating the transcription of interleukin 2. In
T-cells, activation of the T-cell receptor normally increases
intracellular calcium, which acts via calmodulin to activate
calcineurin. Calcineurin then dephosphorylates the transcription
factor nuclear factor of activated T-cells (NFATc), which moves to
the nucleus of the T-cell and increases the activity of genes coding
for IL-2 and related cytokines. Ciclosporin prevents the
dephosphorlyation of NF-AT by binding to cyclophilin. It also
inhibits lymphokine production and interleukin release and,
therefore, leads to a reduced function of effector T-cells. It does
not affect cytostatic activity.
Cyclosporin A affects mitochondria by preventing the
mitochondrial permeability transition pore from opening, thus
inhibiting cytochrome c release, a potent apoptotic stimulation
factor. This is not the primary mechanism of action for clinical
use, but is an important effect for research on apoptosis.
- William F.
Ganong. Review of medical physiology, 22nd edition, Lange
medical books, chapter 27, page 530.
- Henry ML,
Elkhammas EA, Davies EA, Ferguson RM (1995). "A clinical trial
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- Lim HW, De
Windt LJ, Mante J, et al. (April 2000).
"Reversal of cardiac hypertrophy in transgenic disease models by
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Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW
"Cyclophilin: a specific cytosolic binding protein for
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