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Acteoside attenuates TSLP-induced mast cell proliferation via down-regulating MDM2

机译:Acteoside通过下调MDM2减弱TSLP诱导的肥大细胞增殖

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摘要

Acteoside (verbascoside) is extensively distributed in Abeliophyllum distichum and has antimicrobial and anti-inflammatory properties. Thymic stromal lymphopoietin (TSLP) has a pivotal function in the pathogeneses of inflammatory diseases through increasing the mast cell proliferation via the activation of murine double minute 2 (MDM2). Here, we investigate whether acteoside attenuates the MDM2 expression in a TSLP-stimulated human mast cell line (HMC-1 cells). In these cells, TSLP induced the up-regulation of MDM2, and the down-regulation of p53; however, in the TSLP-stimulated HMC-1 cells, the acteoside down-regulated the MDM2 and up-regulated the p53. Increases in the phosphorylation of the single transducer and activation of transcription 6 and 5 via TSLP are decreased by acteoside. The interleukin (IL)-13 (a mast cell growth factor), IL-6, tumor necrosis factor-alpha, and IL-1 beta, levels are significantly reduced by the acteoside in the TSLP-stimulated HMC-1 cells, and the acteoside significantly induces the activation of caspase-3, the cleavage of poly-ADP-ribose polymerase, and the reduction of the procaspase-3 and Bcl2. Furthermore, the mRNA expressions of the TSLP receptor and IL-7 receptor that increase due to TSLP are reduced by the acteoside. In conclusion, these results indicate that acteoside is a specific regulator of MDM2 activation in TSLP-stimulated mast cells, which indicates its potential use for the treatment of mast cell-mediated inflammatory diseases. (C) 2015 Elsevier B.V. All rights reserved.
机译:Acteoside(verbascoside)广泛分布在Abeliophyllum distichum中,具有抗菌和抗炎特性。胸腺基质淋巴细胞生成素(TSLP)在炎症疾病的病原体中起着关键作用,通过激活鼠双分2(MDM2)增强肥大细胞增殖。在这里,我们调查了acteoside是否会减弱TSLP刺激的人类肥大细胞系(HMC-1细胞)中的MDM2表达。在这些细胞中,TSLP诱导了MDM2的上调和p53的下调。然而,在TSLP刺激的HMC-1细胞中,acteoside下调了MDM2并上调了p53。糖苷减少了单个转导子磷酸化的增加以及通过TSLP转录6和5的激活。在TSLP刺激的HMC-1细胞中,Acteoside显着降低了白介素(IL)-13(肥大细胞生长因子),IL-6,肿瘤坏死因子-α和IL-1β的水平。菊糖苷显着诱导caspase-3的活化,多ADP-核糖聚合酶的裂解以及procaspase-3和Bcl2的减少。而且,由于TSLP而增加的TSLP受体和IL-7受体的mRNA表达被洋紫苏苷减少。总之,这些结果表明,acteoside是TSLP刺激的肥大细胞中MDM2活化的特异性调节剂,表明其潜在用途可用于治疗肥大细胞介导的炎性疾病。 (C)2015 Elsevier B.V.保留所有权利。

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