Figure 111

Mechanism of action for cyclosporine (Csa) and tacrolimus (Tac). The common cytoplasmic target for cyclosporine and tacrolimus is calcineurin. After binding to cyclophillin (Cyp), cyclosporine interacts with calcineurin, inhibiting its catalytic domain. Thus dephos-phorylation of transcription factors is prevented, as exemplified by the nuclear factor of activated T lymphocyte (NF-AT). Despite having a different ligand called FK-binding protein (FK-BP), tacrolimus inhibits calcineurin in a similar way. Because phosphorylated transcription factors cannot cross the nuclear membrane, the production of key factors for lymphocyte activation and proliferation (ie, inter-leukin-2, tumor necrosis factor-a, 7 interferon, c-myc, and others) is inhibited [1]. NF-ATc—nuclear factor of activated T-lymphocyte-cytoplasmic form; P—phosphorus; Ca—calcium.

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