Mechanisms of action of cyclosporine

Immunopharmacology. 2000 May;47(2-3):119-25. doi: 10.1016/s0162-3109(00)00192-2.

Abstract

Cyclosporine (cyclosporin A, CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes in activated T cells. It is well established that CsA through formation of a complex with cyclophilin inhibits the phosphatase activity of calcineurin, which regulates nuclear translocation and subsequent activation of NFAT transcription factors. In addition to the calcineurin/NFAT pathway, recent studies indicate that CsA also blocks the activation of JNK and p38 signaling pathways triggered by antigen recognition, making CsA a highly specific inhibitor of T cell activation. Here we discuss the action of CsA on JNK and p38 activation pathways. We also argue the potential of CsA and its natural counterparts as pharmacological probes.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcineurin / drug effects*
  • Calcineurin / metabolism
  • Cyclosporine / pharmacology*
  • Enzyme Activation
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinases / drug effects*
  • Mitogen-Activated Protein Kinases / physiology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Calcineurin