Astragalus polysaccharide modulates ER stress response in an OVA-LPS induced murine model of severe asthma
| Autor: | Jianya Xu, Xia Zhao, Qiong-Qiong Xing, Dou Ding, Yuan Lu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_specialty Chemokine Ovalbumin Active Transport Cell Nucleus Gene Expression Biology Pharmacology Biochemistry 03 medical and health sciences 0302 clinical medicine Polysaccharides Structural Biology Internal medicine medicine Animals Anti-Asthmatic Agents Gene Silencing Interleukin 8 Lung Molecular Biology Mice Inbred BALB C Plant Extracts ATF6 Interleukins Endoplasmic reticulum Mucin Mucins Astragalus Plant General Medicine Immunoglobulin E Endoplasmic Reticulum Stress Asthma CCL20 Mucus 030104 developmental biology Endocrinology CXCL5 030220 oncology & carcinogenesis biology.protein Unfolded protein response Female Goblet Cells |
| Zdroj: | International Journal of Biological Macromolecules. 93:995-1006 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2016.09.058 |
| Popis: | 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, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) 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-κB 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 IRE1β-correlated genes. In summary, APS can have potential pharmaceutical application in treatment of severe asthma. |
| Databáze: | OpenAIRE |
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