期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 93, 期 -, 页码 995-1006出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2016.09.058
关键词
Severe asthma; Astragalus polysaccharide; Endoplasmic reticulum
资金
- Natural Science Foundation of China [81173299, 81473723]
- Natural Science Project of Jiangsu Province, China [15KJA360003]
- Innovation Program for Graduate Students of Jiangsu Province, China [KYZZ15_0269]
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.
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