title: Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in a murine model of neutrophilic asthma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma.
authors.affiliation: a Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Qinyue
authors.initials: Q
authors.lastname: Guo
authors.affiliation: b Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Li
authors.affiliation: b Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Liu
authors.affiliation: c Department of Endocrinology , the Affiliated Guangren Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: d Department of Respiratory , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: d Department of Respiratory , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: d Department of Respiratory , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D051701:Activating Transcription Factor 4 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014415:Tunicamycin / Q000494:pharmacology*; D019892:eIF-2 Kinase / Q000187:drug effects / Q000378:metabolism
chemical_list: D051701:Activating Transcription Factor 4; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D051742:Transcription Factor CHOP; D014409:Tumor Necrosis Factor-alpha; D014415:Tunicamycin; D019892:eIF-2 Kinase
keywords: Airway inflammation; ER stress; PERK-ATF4-CHOP signaling; inflammatory cytokine; neutrophilic asthma; tunicamycin