Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling

Clin Immunol. 2024 Jun:263:110228. doi: 10.1016/j.clim.2024.110228. Epub 2024 Apr 23.

Abstract

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-β1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.

Keywords: Airway remodeling; Asthma; Eosinophil peroxidase; Epithelial-mesenchymal transition; Inflammatory.

MeSH terms

  • ADAM Proteins
  • Adult
  • Airway Remodeling*
  • Asthma* / immunology
  • Asthma* / metabolism
  • Asthma* / pathology
  • Asthma* / physiopathology
  • Bronchi* / pathology
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Chromones / pharmacology
  • Cytokines / metabolism
  • Eosinophil Peroxidase* / metabolism
  • Epithelial Cells* / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Interleukin-5 / metabolism
  • Male
  • Middle Aged
  • Morpholines / pharmacology
  • Thymic Stromal Lymphopoietin
  • Transforming Growth Factor beta1* / metabolism

Substances

  • ADAM33 protein, human
  • TSLP protein, human
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • IL5 protein, human
  • TGFB1 protein, human