Molecular actions of calcineurin inhibitors.
The immunosuppressive drugs cyclosporin A and FK-506, also called calcineurin inhibitors, have been useful for treating immune system-mediated diseases and have truly revolutionized allograft transplantation. Both drugs block T-cell proliferation by mechanisms that involve the inhibition of the key signaling phosphatase calcineurin, hence, the name calcineurin inhibitors. The inhibition of calcineurin activation by cyclosporin A and FK-506 blocks T-cell receptor-mediated production of interleukin-2 (IL-2), a growth factor critical for T-cell proliferation. Recent studies, however, suggest that the effects of the drugs are not limited to blocking calcineurin activation and IL-2 production. This review discusses the molecular actions of cyclosporin A and FK-506.
Hamawy
Majed M
MM
Department of Surgery, Division of Transplantation, University of Wisconsin, H4/749, CSC 600 Highland Avenue, Madison, WI 53792, USA. hamawy@surgery.wisc.edu
D019703:Calcineurin / Q000187:drug effects; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016559:Tacrolimus / Q000493:pharmacokinetics*; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus