Tsuji R F, Yamamoto M, Nakamura A, Kataoka T, Magae J, Nagai K, Yamasaki M
Department of Agricultural Chemistry, University of Tokyo, Japan.
J Antibiot (Tokyo). 1990 Oct;43(10):1293-301. doi: 10.7164/antibiotics.43.1293.
The immunosuppressive effects of prodigiosin 25-C were studied in comparison with FK506. Both prodigiosin 25-C and FK506 suppressed T cell proliferation in response to concanavalin A (con A) or phytohemagglutinin (PHA) more significantly than that to lipopolysaccharide. However, prodigiosin 25-C inhibited con A-mediated mitogenic response more strongly than PHA-mediated one. FK506 showed no selectivity among those responses. In addition, when higher concentration of con A was used an inhibitory effect of prodigiosin 25-C became more evident whereas that of FK506 became less evident. Furthermore, prodigiosin 25-C affected neither interleukin-2 (IL-2) production nor IL-2 receptor (IL-2R) and transferrin receptor (TF-R) expression in vitro, though FK506 extensively inhibited IL-2 production and significantly suppressed IL-2R and TF-R expression. When comparing the effects of prodigiosin 25-C and FK506 in vivo by injecting antigens of different nature to a mouse, prodigiosin 25-C selectively inhibited cytotoxic T lymphocyte (CTL) activity induced by an allogenic mastocytoma, P815, without affecting production of antibody against a thymus dependent (TD) antigen, sheep red blood cell (SRBC). On the contrary, FK506 significantly inhibited both CTL induction and the antibody production. When Brucella abortus, a thymus independent (TI) antigen, and SRBC were simultaneously challenged to a mouse, neither prodigiosin 25-C nor FK506 affected antibody production against the TI antigen while the effect on the TD antigen were the same as described above. The present results revealed the unique immunosuppressive property of prodigiosin 25-C which was different from that of FK506.
研究了灵菌红素25-C与他克莫司（FK506）相比的免疫抑制作用。灵菌红素25-C和FK506对刀豆球蛋白A（Con A）或植物血凝素（PHA）刺激的T细胞增殖的抑制作用均比脂多糖刺激的更为显著。然而，灵菌红素25-C对Con A介导的有丝分裂反应的抑制作用比对PHA介导的更为强烈。FK506在这些反应中没有表现出选择性。此外，当使用更高浓度的Con A时，灵菌红素25-C的抑制作用变得更加明显，而FK506的抑制作用则变得不那么明显。此外，灵菌红素25-C在体外对白细胞介素-2（IL-2）的产生、IL-2受体（IL-2R）和转铁蛋白受体（TF-R）的表达均无影响，而FK506则广泛抑制IL-2的产生，并显著抑制IL-2R和TF-R的表达。通过向小鼠注射不同性质的抗原比较灵菌红素25-C和FK506在体内的作用时，灵菌红素25-C选择性地抑制同种异体肥大细胞瘤P815诱导的细胞毒性T淋巴细胞（CTL）活性，而不影响针对胸腺依赖性（TD）抗原绵羊红细胞（SRBC）的抗体产生。相反，FK506显著抑制CTL诱导和抗体产生。当将胸腺非依赖性（TI）抗原流产布鲁氏菌和SRBC同时攻击小鼠时，灵菌红素25-C和FK506均不影响针对TI抗原的抗体产生，而对TD抗原的作用与上述相同。目前的结果揭示了灵菌红素25-C独特的免疫抑制特性，这与FK506不同。
