Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis

• Published in: PloS one 2016-12, Vol.11 (12), p.e0167729-e0167729
• Main Authors: Kida, Taiki, Ayabe, Shinya, Omori, Keisuke, Nakamura, Tatsuro, Maehara, Toko, Aritake, Kosuke, Urade, Yoshihiro, Murata, Takahisa
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Asthma; Biology and Life Sciences; Bleomycin; Bleomycin - adverse effects; Chemokine CCL2 - genetics; Collagen; Collagen - metabolism; Critical care; Cyclooxygenase 2 - genetics; Cyclooxygenase-2; Cytokines; Disease; Disease control; Disease Models, Animal; Fibroblasts; Fibrosis; Gene expression; Gene Knockout Techniques; Infiltration; Inflammation; Isomerases - genetics; Leukocytes (neutrophilic); Life sciences; Lung - metabolism; Lung - pathology; Lung diseases; Lungs; Macrophages; Macrophages - metabolism; Medicine; Medicine and Health Sciences; Metastases; Mice; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Neutrophil Infiltration - drug effects; Neutrophils; Ostomy; Pathogenesis; Permeability; Pneumonia - chemically induced; Pneumonia - genetics; Pneumonia - metabolism; Prostaglandin D2; Prostaglandin D2 - metabolism; Prostaglandins; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rodents; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167729

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.