Mechanisms of action of cyclosporine.
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.
Matsuda
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Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan.
Koyasu
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D000818:Animals; D019703:Calcineurin / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin