title: Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.
abstract: Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Kida
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ayabe
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Omori
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Toko
authors.initials: T
authors.lastname: Maehara
authors.affiliation: International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.affiliation: International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D018932:Chemokine CCL2 / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D003094:Collagen; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C545516:HPGDS protein, mouse; D015230:Prostaglandin D2