Epithelial cell-derived prostaglandin D 2 inhibits chronic allergic lung inflammation in mice

FASEB J. 2019 Jul;33(7):8202-8210. doi: 10.1096/fj.201802817R. Epub 2019 Apr 24.

Abstract

The precise role of prostaglandin D (PGD)2 in allergic lung inflammation remains controversial. Here, we aimed to clarify the role of PGD2 in chronic allergic lung inflammation using hematopoietic PGD synthase (H-PGDS)-deficient mice. Repeated intranasal administration of ovalbumin (OVA) resulted in eosinophilic infiltration and mucin production in the lungs of wild type (WT) mice, leading to respiratory dysfunction. H-PGDS deficiency exacerbated these effects, which were accompanied by increased mRNA expression of TNF-α and eosinophil chemoattractants. The bronchial epithelium expressed both H-PGDS and TNF-α in the inflamed WT lung, and H-PGDS deficiency increased TNF-α expression further. In cultured bronchial tissue of WT mice, treatment with LPS elevated mRNA expression of TNF-α and eosinophil chemoattractants. H-PGDS deficiency promoted the expression of these factors, which was inhibited by treatment with PGD2 receptor, D prostanoid (DP) receptor agonist, or PGD2 metabolite 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2). Treatment with TNF-α receptor antibody inhibited eosinophil chemoattractant expression. In vivo, administration of DP agonist or 15d-PGJ2 inhibited OVA-induced allergic lung inflammation. Bronchial epithelial cell-derived PGD2 attenuated lung eosinophilic infiltration with chronic allergic inflammation; these phenomena are at least partly attributed to the inhibition of TNF-α production via DP activation or 15-deoxy-Δ12,14-PGJ2 signaling.-Maehara, T., Nakamura, T., Maeda, S., Aritake, K., Nakamura, M., Murata, T. Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice.

Keywords: 15d-PGJ; DP receptor; allergy; eosinophil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / genetics
  • Asthma / metabolism*
  • Chronic Disease
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Gene Expression Regulation
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Lipopolysaccharides / toxicity
  • Lung / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Knockout
  • Pneumonia / chemically induced
  • Pneumonia / genetics
  • Pneumonia / metabolism*
  • Prostaglandin D2 / genetics
  • Prostaglandin D2 / metabolism*
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Intramolecular Oxidoreductases
  • Prostaglandin D2