Azithromycin differentially affects the IL-13-induced expression profile in human bronchial epithelial cells

Pulm Pharmacol Ther. 2016 Aug;39:14-20. doi: 10.1016/j.pupt.2016.05.005. Epub 2016 May 28.

Abstract

The T helper 2 (Th2) cytokine interleukin(IL)-13 is a central regulator in goblet cell metaplasia and induces the recently described Th2 gene signature consisting of periostin (POSTN), chloride channel regulator 1 (CLCA1) and serpin B2 (SERPINB2) in airway epithelial cells. This Th2 gene signature has been proposed as a biomarker to classify asthma into Th2-high and Th2-low phenotypes. Clinical studies have shown that the macrolide antibiotic azithromycin reduced clinical symptoms in neutrophilic asthma, but not in the classical Th2-mediated asthma despite the ability of azithromycin to reduce IL-13-induced mucus production. We therefore hypothesize that azithromycin differentially affects the IL-13-induced expression profile. To investigate this, we focus on IL-13-induced mucin and Th2-signature expression in human bronchial epithelial cells and how this combined expression profile is affected by azithromycin treatment. Primary bronchial epithelial cells were differentiated at air liquid interface in presence of IL-13 with or without azithromycin. Azithromycin inhibited IL-13-induced MUC5AC, which was accompanied by inhibition of IL-13-induced CLCA1 and SERPINB2 expression. In contrast, IL-13-induced expression of POSTN was further increased in cells treated with azithromycin. This indicates that azithromycin has a differential effect on the IL-13-induced Th2 gene signature. Furthermore, the ability of azithromycin to decrease IL-13-induced MUC5AC expression may be mediated by a reduction in CLCA1.

Keywords: Asthma; Azithromycin; Azithromycin dihydrate (PubChem CID: 441190); Human bronchial epithelial cells; Interleukin-13; Th2 gene signature.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Azithromycin / pharmacology*
  • Bronchi / cytology
  • Bronchi / drug effects*
  • Cell Adhesion Molecules / genetics
  • Cells, Cultured
  • Chloride Channels / genetics
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism*
  • Mucin 5AC / metabolism
  • Mucins / metabolism
  • Plasminogen Activator Inhibitor 2 / genetics
  • Th2 Cells / immunology

Substances

  • Anti-Bacterial Agents
  • CLCA1 protein, human
  • Cell Adhesion Molecules
  • Chloride Channels
  • Interleukin-13
  • MUC5AC protein, human
  • Mucin 5AC
  • Mucins
  • POSTN protein, human
  • Plasminogen Activator Inhibitor 2
  • Azithromycin