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: Taiki Kida, Shinya Ayabe, Keisuke Omori, Tatsuro Nakamura, Toko Maehara, Kosuke Aritake, Yoshihiro Urade, Takahisa Murata
• Journal: PloS one (PLoS One) Vol. 11 Issue 12 Pg. e0167729 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27992456 (Publication Type: Journal Article)

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Tumor Necrosis Factor-alpha
• Bleomycin
• Collagen
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Isomerases
• Intramolecular Oxidoreductases
• HPGDS protein, mouse
• Prostaglandin D2

Topics

• Animals
• Bleomycin (adverse effects)
• Chemokine CCL2 (genetics)
• Collagen (metabolism)
• Cyclooxygenase 2 (genetics)
• Disease Models, Animal
• Gene Knockout Techniques
• Intramolecular Oxidoreductases
• Isomerases (genetics)
• Lung (metabolism, pathology)
• Macrophages (metabolism)
• Mice
• Neutrophil Infiltration (drug effects)
• Pneumonia (chemically induced, genetics, metabolism)
• Prostaglandin D2 (metabolism)
• Pulmonary Fibrosis (chemically induced, genetics, metabolism, pathology)
• Tumor Necrosis Factor-alpha (genetics)