Matsuda S, Koyasu S
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan.
Immunopharmacology. 2000 May;47(2-3):119-25. doi: 10.1016/s0162-3109(00)00192-2.
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.
环孢素（环孢菌素A，CsA）具有强大的免疫抑制特性，这反映出它能够阻断活化T细胞中细胞因子基因的转录。众所周知，CsA通过与亲环蛋白形成复合物来抑制钙调神经磷酸酶的磷酸酶活性，而钙调神经磷酸酶可调节核因子活化T细胞（NFAT）转录因子的核转位及随后的激活。除了钙调神经磷酸酶/NFAT途径外，最近的研究表明，CsA还能阻断由抗原识别触发的JNK和p38信号通路的激活，这使得CsA成为T细胞激活的高度特异性抑制剂。在此，我们讨论CsA对JNK和p38激活途径的作用。我们还探讨了CsA及其天然类似物作为药理学探针的潜力。
