Preferential generation of 15-HETE-PE induced by IL-13 regulates goblet cell differentiation in human airway epithelial cells

Jinming Zhao*, Yoshinori Minami, Emily Etling, John M. Coleman, Sarah N. Lauder, Victoria Tyrrell, Maceler Aldrovandi, Valerie O'Donnell, Hans Erik Claesson, Valerian Kagan, Sally Wenzel

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Type 2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase-1 (15LO1) is induced by the type 2 cytokine IL-13 in human airway epithelial cells (HAECs) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15- HETE-phosphatidylethanolamine (15-HETE-PE), and 13-hydroxyoctadecadienoic acid (13-HODE). In this study, we investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, as well as its influence on goblet cell differentiation in HAECs. Primary HAECs obtained from bronchial brushings of asthmatic and healthy subjects were cultured under air-liquid interface culture supplemented with arachidonic acid and linoleic acid (10 mMeach) and exposed to IL-13 for 7 days. Short interfering RNA transfection and 15LO1 inhibition were applied to suppress 15LO1 expression and activity. IL-13 stimulation induced expression of 15LO1 and preferentially generated 15-HETE-PE in vitro, both of which persisted after removal of IL-13. 15LO1 inhibition (by short interfering RNA and chemical inhibitor) decreased IL-13-induced forkhead box protein A3 (FOXA3) expression and enhanced FOXA2 expression. These changes were associated with reductions in both mucin 5AC and periostin. Exogenous 15-HETE-PE stimulation (alone) recapitulated IL-13-induced FOXA3, mucin 5AC, and periostin expression. The results of this study confirm the central importance of 15LO1 and its primary product, 15-HETE-PE, for epithelial cell remodeling in HAECs.

Original languageEnglish (US)
Pages (from-to)692-701
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume57
Issue number6
DOIs
StatePublished - Dec 2017

Keywords

  • 15-lipoxygenase-1
  • Asthma
  • Eicosanoid
  • Mucus hypersecretion
  • Phospholipid

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Zhao, J., Minami, Y., Etling, E., Coleman, J. M., Lauder, S. N., Tyrrell, V., Aldrovandi, M., O'Donnell, V., Claesson, H. E., Kagan, V., & Wenzel, S. (2017). Preferential generation of 15-HETE-PE induced by IL-13 regulates goblet cell differentiation in human airway epithelial cells. American journal of respiratory cell and molecular biology, 57(6), 692-701. https://doi.org/10.1165/rcmb.2017-0031OC