*4.6. Mechanism of Action of Cyclosporin A (CsA)*

As a calcineurin inhibitor, cyclosporin A (CsA) binds to cyclophilins (Cyps). Cyps are the binding partner proteins of CsA, which, as host cell receptors for CsA, mediate the immunosuppressive action of CsA, by inhibiting calcineurin (Figure 1) [11]. Cyclophilins belong to the immunophilins, and the most abundant cyclophilin is Cyclophilin A (CypA), which is widely distributed in almost all tissues and accounts for 0.1–0.4% of the total protein content in a cell [45]. It also is abundant in the cytosolic extract from lymphocytes, and has a high affinity for CsA. CypA acts as an acceleration factor in protein folding and assembly [45].

Inflammatory stimuli [46,47], oxidative stress [46,48] and activated platelets [49] result in cellular secretion of CypA. Following stimulation with reactive oxygen species (ROS), CypA was detectable at the plasma membrane of vascular smooth muscle cells within 30 min of stimulation [46]. When CsA inhibits Cyps, several important effects occur, which are summarized below:
