Astragalus polysaccharide modulates ER stress response in an OVA-LPS induced murine model of severe asthma
Astragalus polysaccharide modulates ER stress response in an OVA-LPS induced murine model of severe asthma
复制标题
黄芪多糖调节 OVA-LPS 诱导的严重哮喘小鼠模型中的 ER 应激反应
DOI：
10.1016/j.ijbiomac.2016.09.058
复制
发表时间：
2016-12-01
影响因子：
8.2
通讯作者：
Zhao, Xia
中科院分区：
文献类型：
--
作者：
Lu, Yuan;Xing, Qiong-Qiong;Zhao, Xia
内质网（ER）应激在严重哮喘的发病机制中起关键作用。黄芪多糖（Astragalus polysaccharide，APS）是黄芪的主要生物活性成分，具有免疫调节和抗炎作用，并能抑制2型糖尿病等慢性疾病的内质网应激。然而，APS在治疗严重哮喘中的药学应用尚不清楚。本文获得的结果表明，APS通过降低Cxc 15、118和趋化因子（C-C基序）配体20（Cc 120）的mRNA水平以及IL 13 RA和IL 17 RA的蛋白水平，显著减弱嗜酸性粒细胞和嗜酸性粒细胞主导的气道炎症。APS还通过降低ER应激标志物如C/EBP同源蛋白（CHOP）的水平来抑制未折叠蛋白反应的激活，这与PERK磷酸化的减少有关。此外，APS基本上阻断了ATF 6和NF-κ B p65的核转位。有趣的是，我们观察到APS通过降低粘蛋白（MUC）5AC和MUC 5 B的水平来显著抑制粘液高分泌，这可能是由于通过抑制IRE 1 β相关基因的表达来抑制杯状细胞分化。综上所述，黄芪多糖在治疗重症哮喘方面具有潜在的药学应用价值。(C)2016爱思唯尔B. V.保留所有权利。
Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the, pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, 118, and chemokine (C-C motif) ligand 20 (Cc120) and the protein levels of IL13RA and IL17RA. APS also inhibits the activation of unfolded protein response by decreasing the levels of ER stress markers such as C/EBP homologous protein (CHOP), which was associated with a reduction of PERK phosphorylation. Moreover, APS substantially blocks the nuclear translocation of ATF6 and NF-kappa B p65. Interestingly, we observed that APS markedly suppresses mucus hypersecretion by decreasing the levels of mucin (MUC) 5AC and MUC5B, which might be due to inhibition of goblet cells differentiation by suppressing the expression of IRE1 beta-correlated genes. In summary, APS can have potential pharmaceutical application in treatment of severe asthma. (C) 2016 Elsevier B.V. All rights reserved.