Mizushima Y, Kosaka H, Sakuma S, Kanda K, Itoh K, Osugi T, Mizushima A, Hamaoka T, Yoshida H, Sobue K
Department of Oncogenesis, Institute for Cancer Research, Osaka.
J Biochem. 1987 Nov;102(5):1193-201. doi: 10.1093/oxfordjournals.jbchem.a122158.
The in vitro stimulation of murine splenic T lymphocytes with concanavalin A (Con A) produced interleukin 2 (IL2). The addition of cyclosporin A (CsA) to the culture resulted in complete inhibition of IL2 production. The Con A stimulation of T lymphocytes induced the breakdown of phosphatidylinositol into inositol trisphosphate and diacylglycerol, each of which could function as the second messengers in the subsequent signal transduction pathway. CsA did not inhibit the production of inositol (poly)phosphates. Further, CsA did not affect Ca2+-calmodulin functions; a) the redistribution of various cytoskeletal proteins as well as Con A-receptor aggregation, and b) the cytosolic Ca2+-calmodulin-dependent enzyme activities. Moreover, the activity of protein kinase C, which has been accepted to be the target of diacylglycerol, was not influenced in the presence of CsA. While the above steps of signal transduction are bypassed by synergy between calcium ionophore and phorbol ester, T lymphocyte activation which was induced by such stimuli was completely inhibited by CsA. These results indicate that CsA does not influence early steps of T lymphocyte activation as bypassed by calcium ionophore and phorbol ester, but rather inhibits later step(s) subsequent to the activation of protein kinase C and Ca2+-calmodulin.
用刀豆蛋白A（Con A）对小鼠脾T淋巴细胞进行体外刺激可产生白细胞介素2（IL2）。向培养物中添加环孢素A（CsA）会导致IL2产生完全受到抑制。Con A对T淋巴细胞的刺激诱导磷脂酰肌醇分解为肌醇三磷酸和二酰基甘油，它们均可在随后的信号转导途径中作为第二信使发挥作用。CsA并不抑制肌醇（多）磷酸的产生。此外，CsA不影响Ca2 + -钙调蛋白的功能：a）各种细胞骨架蛋白的重新分布以及Con A受体的聚集，以及b）胞质Ca2 + -钙调蛋白依赖性酶的活性。此外，已被认为是二酰基甘油作用靶点的蛋白激酶C的活性在有CsA存在的情况下并未受到影响。虽然钙离子载体与佛波酯之间的协同作用绕过了上述信号转导步骤，但由这种刺激诱导的T淋巴细胞活化被CsA完全抑制。这些结果表明，CsA并不影响钙离子载体与佛波酯所绕过的T淋巴细胞活化的早期步骤，而是抑制蛋白激酶C和Ca2 + -钙调蛋白活化之后的后期步骤。
