Cyclosporin A, an Immunosuppressant, Binds to the Cyclophilin and Inhibits Calcineurin Phosphatase Activity

Immunosuppressive agents, also known as immunosuppressants and antirejection medications, can inhibit or prevent activity of the immune system. Immunosuppression is a reduction of the activation or efficacy of the immune system. Immunosuppressants have many uses, such as preventing rejection of transplanted organs and tissues, treating autoimmune diseases or other non-autoimmune inflammatory diseases. Immunosuppressants and FK506 bind to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK506-binding proteins (FKBPs). Calcineurin is expressed in T cells, and its activity can be measured in cell lysates.

Cyclosporin A (also known as Cyclosporine A, Ciclosporin A or CsA) is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of calcineurin. And Cyclosporin A is used in allografting, especially in organ transplantation. In vitro, the complexes of Cyclosporin A-cyclophilin and FK506-FKBP-12 bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase. In addition, this compound is a valuable probe for studying T-cell signal transduction, and Cyclosporin A also inhibits Ca²⁺-dependent activation pathways that lead to transcription of lymphokine genes. Furthermore, in mouse model of pleurisy induced by carrageenan, Cyclosporin A downregulates CD11a/CD18 adhesion molecule in the lungs, as well as TNF-α and IL-1β in the fluid leakage of the pleural cavity.

In summary, Cyclosporin A, an immunosuppressant, binds to the cyclophilin and inhibits calcineurin phosphatase activity.

References:

[1] D A Fruman, et al. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686-90.

[2] Eduardo Monguilhott Dalmarco, et al. Cell Adh Migr. Oct-Dec 2008;2(4):231-5.