PP4 deficiency contributes to DEP exacerbated epithelial barrier dysfunction and airway inflammation in asthmatic patients

Abstract Diesel exhaust particles (DEP) emitted from motor vehicle or heavy-duty industries is thought to be the major source of air pollutants that lead rapid increase and worsening allergic disease, such as asthma. In asthma, exposure DEP has been linked aberrant epithelial barrier integrity, which leads promotion allergen delivery into subepithelia induced alarmins (IL-33, IL-25 thymic stromal lymphopoietin (TSLP)) release promote Th2-mediated inflammation. However, it still not known detail mechanism airway in response DEP. this study, we fund PP4 expression was decreased DEP-challenged human bronchial cells air-pollution animal model. Moreover, silencing E-cadherin integrity through activated Src kinase increased Slug. Sequentially, transactivating EGFR phosphorylation led alarmin synthesis. Overexpression wild type, but phosphatase mutant, prevented DEP-induced loss release, suggested activity critical maintain production. Primary (HBECs) mild severe asthmatic patients showed a significantly low TJ ALI cultures DEP, compared with HBECs healthy subjects. Our data demonstrate causes significant reduction leading function might accelerate allergen-induced inflammatory Supported by grants (MOST 110-2320-B-038-065-MY3) Ministry Science Technology Taiwan.