Description
Use Cyclosporin A to suppress T cell activation and proliferation through calcineurin inhibition (IC50 = 7 nM). Calcineurin is a Ca2+- and calmodulin-dependent serine/threonine protein phosphatase involved in interleukin-2 transcription and T cell activation (Hermann-Kleiter & Baier. Blood, 2010). Cyclosporin A binds to a cytosolic protein called cyclophilin to form a complex that inhibits calcineurin (Handschumacher et al. Science, 1984) and its downstream effects. This immunosuppressive agent has also been shown to inhibit cytochrome P-450 3A (CYP3A) in human liver microsomes (Ki = 0.98 μM; Amundsen et al. Drug Metab Dispos, 2012).
Cyclosporin A has been used for:
DIFFERENTIATION
· Stimulate colony growth of Thy-1.1lowSca-1+Lin- mouse HSPCs in low concentrations in combination with growth factors but inhibit colony growth at high concentrations (Perry et al. Cell Transplant, 1999).
· Promote cell survival of neural stem and progenitor cells in mice through a calcineurin-independent pathway (Hunt et al. J Neurosci, 2010; Sachewsky et al. Dis Model Mech, 2014).
IMMUNOLOGY
· Suppress T cell activation and proliferation through the inhibition of calcineurin/nuclear factor of activated T cells (NFAT) signaling (Ho et al. Immunopathol, 1996).
· Interfere with T cell maturation and selection in the thymus and with deletion of self-reactive cells (Damoiseaux et al. Clin Immunol Immunopathol, 1997; Jenkins et al. Science, 1988).
· Prevent rejection of allografts in experimental animal models (Lim & White. Cyclosporin, 1989).
DISEASE MODELING
· Inhibit formation of lesions and development of disease in mouse and rat models of rheumatoid arthritis (Pozo et al. Semin Arthritis Rheum, 1992; Takagishi et al. Agents Actions, 1992).
· Decrease levels of pro-inflammatory cytokines, reduce lymphocyte infiltration, and improve organ pathology in a mouse model of acute graft versus host disease (Corbett et al. Transpl Immunol, 2021).
