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Immunomodulatory compounds from Pestalotiopsis leucothes, an endophytic fungus from Tripterygium wilfordii

机译:来自雷公藤的内生真菌Pestalotiopsis leucothes的免疫调节化合物

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The immunomodulatory effects of three compounds designated BS, GS, and YS produced by Pestalotiopsis leucothes, an endophytic fungus isolated from Tripterygium wilfordii, were evaluated. The 50% inhibition concentration (IC50) value of BS in the proliferative assay with various stimulating agents such as phytohemagglutinin-M (PHA-M), phorbol myristate acetate (PMA)/ionomycin, mixed lymphocyte reaction (MLR) and poke weed mitogen (PWM) was 0.35, 1.6, 0.8 and 5.4 mu g/ml, respectively. In addition, BS significantly inhibited the production of cytokines such as interleukin (IL)-1 beta, IL-2, interferon (IFN)-gamma and tumor necrosis factor (TWF)-alpha, by peripheral blood mononuclear cells (PBMNC) and soluble IL-2 receptor expression at concentrations greater than 1 mu g/ml. Inhibition of PHA stimulated PBMNC proliferation and IL-2 and sIL-2R production by BS indicates that it is a T-cell specific immunosuppressant. However, BS also moderately inhibited immunoglobulin (Ig) G and M at concentrations greater than 1 mu g/ml suggesting that it also has B cell immunosuppressive effects. YS was 10% less active than BS in all assay systems. In contrast, GS exhibited both suppression and enhancement of PBMNC proliferation in the presence of various stimulants. However, GS inhibited PWM stimulated PBMNC proliferation and IL-4 and IgG and IgM production at concentrations above 1 mu g/ml. All three fungal compounds altered the percentage of T-lymphocyte subpopulations only at high concentrations. Cell viability was not affected at the immunosuppressive concentrations of these compounds. In conclusion, work from our laboratory has identified three potentially potent immunomodulatory compounds from P. leucothes. These compounds have variable effects on T- and B-cells and monocytes. They may partially explain the imimmosuppressive activity of T. wilfordii. In addition, they may represent a new source of immumomodulatory compounds for the treatment of human immune mediated diseases. (c) 2005 Elsevier Inc. All rights reserved.
机译:评估了由白粉虱(Pestalotiopsis leucothes)(一种从雷公藤提取物分离的内生真菌)产生的三种化合物的免疫调节作用,分别命名为BS,GS和YS。在各种刺激剂如植物血凝素-M(PHA-M),佛波肉豆蔻酸酯乙酸盐(PMA)/离子霉素,混合淋巴细胞反应(MLR)和oke杂促分裂素( PWM)分别为0.35、1.6、0.8和5.4μg / ml。此外,BS通过外周血单核细胞(PBMNC)显着抑制细胞因子的产生,例如白介素(IL)-1 beta,IL-2,干扰素(IFN)-γ和肿瘤坏死因子(TWF)-α浓度大于1μg / ml的IL-2受体表达。 BS抑制PHA刺激的PBMNC增殖以及IL-2和sIL-2R的产生表明它是T细胞特异性免疫抑制剂。但是,BS还以大于1μg / ml的浓度适度抑制免疫球蛋白(Ig)G和M,表明它也具有B细胞免疫抑制作用。在所有测定系统中,YS的活性均比BS低10%。相反,在各种刺激剂的存在下,GS表现出抑制和增强PBMNC增殖的作用。然而,当浓度高于1μg / ml时,GS抑制PWM刺激的PBMNC增殖以及IL-4和IgG和IgM的产生。所有这三种真菌化合物仅在高浓度下才改变T淋巴细胞亚群的百分比。在这些化合物的免疫抑制浓度下,细胞活力不受影响。总之,我们实验室的工作已经从隐色假单胞菌中鉴定出三种潜在的有效免疫调节化合物。这些化合物对T细胞和B细胞以及单核细胞具有可变的作用。他们可能部分解释了维尔氏锥虫的免疫抑制活性。此外,它们可能代表用于治疗人类免疫介导疾病的免疫调节化合物的新来源。 (c)2005 Elsevier Inc.保留所有权利。

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