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

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-Δ^12,14-PGJ₂ (15d-PGJ₂). Treatment with TNF-α receptor antibody inhibited eosinophil chemoattractant expression. <i>In vivo</i>, 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 <i>via</i> DP activation or 15-deoxy-Δ^12,14-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.