Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice

The precise role of prostaglandin D (PGD)(2) in allergic lung inflammation remains controversial. Here, we aimed to clarify the role of PGD(2) 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-alpha and eosinophil chemoattractants. The bronchial epithelium expressed both H-PGDS and TNF-alpha in the inflamed WT lung, and H-PGDS deficiency increased TNF-alpha expression further. In cultured bronchial tissue of WT mice, treatment with LPS elevated mRNA expression of TNF-alpha and eosinophil chemoattractants. H-PGDS deficiency promoted the expression of these factors, which was inhibited by treatment with PGD(2) receptor, D prostanoid (DP) receptor agonist, or PGD(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). Treatment with TNF-alpha receptor antibody inhibited eosinophil chemoattractant expression. In vivo, administration of DP agonist or 15d-PGJ(2) inhibited OVA-induced allergic lung inflammation. Bronchial epithelial cell-derived PGD(2) attenuated lung eosinophilic infiltration with chronic allergic inflammation; these phenomena are at least partly attributed to the inhibition of TNF-alpha production via DP activation or 15-deoxy-Delta(12,14)-PGJ(2) signaling.-Maehara, T., Nakamura, T., Maeda, S., Aritake, K., Nakamura, M., Murata, T. Epithelial cell-derived prostaglandin D-2 inhibits chronic allergic lung inflammation in mice.