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Publication : Epithelial cell-derived prostaglandin D<sub>2</sub> inhibits chronic allergic lung inflammation in mice.

First Author  Maehara T Year  2019
Journal  FASEB J Volume  33
Issue  7 Pages  8202-8210
PubMed ID  31018708 Mgi Jnum  J:292362
Mgi Id  MGI:6448878 Doi  10.1096/fj.201802817R
Citation  Maehara T, et al. (2019) Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice. FASEB J 33(7):8202-8210
abstractText  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-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 PGD2 receptor, D prostanoid (DP) receptor agonist, or PGD2 metabolite 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2). Treatment with TNF-alpha 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-alpha production via DP activation or 15-deoxy-Delta(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.
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