Qinyue Guo1, Huixia Li2, Jiali Liu2, Lin Xu3, Lan Yang4, Zhongmin Sun4, Bo Zhou4. 1. a Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China. 2. b Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University , Xi'an , Shaanxi , China. 3. c Department of Endocrinology , the Affiliated Guangren Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China. 4. d Department of Respiratory , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
Abstract
INTRODUCTION: Endoplasmic reticulum (ER) stress has been considered to be an important regulator of airway inflammation in the pathogenesis of bronchial asthma, but the mechanism of ER stress involved in neutrophilic asthma remain not fully understood. METHODS: Tunicamycin is a mixture of homologous nucleoside antibiotics, which is used to induce ER stress. In the present study, Tunicamycin was administered to mouse bronchial epithelial cells and a neutrophilic asthma model (OVALPS-OVA mice), and ER stress indicators and inflammatory cytokines were measured by Western blotting and Elisa. RESULTS: Tunicamycin not only induced ER stress in mouse bronchial epithelial cells, but also increased expression of inflammation indicators such as IL-6, IL-8, and TNF-α via PERK-ATF4-CHOP signaling. Additionally, the phosphorylation of PERK and the expression levels of ATF4 and CHOP proteins and inflammatory cytokines (IL-6, IL-8 and TNF-α) were elevated in the lung tissue of OVALPS-OVA mice. Administering tunicamycin further increased protein expression levels of ER stress indicators and inflammatory cytokines, and resulted in more severe asthma phenotypes in OVALPS-OVA mice, suggesting that PERK-ATF4-CHOP signaling is associated with airway inflammation in neutrophil-dominant asthma. CONCLUSIONS: These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma.
INTRODUCTION: Endoplasmic reticulum (ER) stress has been considered to be an important regulator of airway inflammation in the pathogenesis of bronchial asthma, but the mechanism of ER stress involved in neutrophilic asthma remain not fully understood. METHODS:Tunicamycin is a mixture of homologous nucleoside antibiotics, which is used to induce ER stress. In the present study, Tunicamycin was administered to mouse bronchial epithelial cells and a neutrophilic asthma model (OVALPS-OVA mice), and ER stress indicators and inflammatory cytokines were measured by Western blotting and Elisa. RESULTS:Tunicamycin not only induced ER stress in mouse bronchial epithelial cells, but also increased expression of inflammation indicators such as IL-6, IL-8, and TNF-α via PERK-ATF4-CHOP signaling. Additionally, the phosphorylation of PERK and the expression levels of ATF4 and CHOP proteins and inflammatory cytokines (IL-6, IL-8 and TNF-α) were elevated in the lung tissue of OVALPS-OVA mice. Administering tunicamycin further increased protein expression levels of ER stress indicators and inflammatory cytokines, and resulted in more severe asthma phenotypes in OVALPS-OVA mice, suggesting that PERK-ATF4-CHOP signaling is associated with airway inflammation in neutrophil-dominant asthma. CONCLUSIONS: These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma.
Authors: Yu-Fan Yang; Hui Wang; Nan Song; Ya-Hui Jiang; Jun Zhang; Xiao-Wen Meng; Xiao-Mei Feng; Hong Liu; Ke Peng; Fu-Hai Ji Journal: J Inflamm Res Date: 2021-03-31
Authors: Helena Crisford; Elizabeth Sapey; Geraint B Rogers; Steven Taylor; Prasad Nagakumar; Ravi Lokwani; Jodie L Simpson Journal: Thorax Date: 2021-02-25 Impact factor: 9.139