Prostaglandin D₂ Attenuates Lipopolysaccharide-Induced Acute Lung Injury through the Modulation of Inflammation and Macrophage Polarization

Acute lung injury (ALI) is a well-known respiratory disease and a leading cause of death worldwide. Despite advancements in the medical field, developing complete treatment strategies against this disease is still a challenge. In the current study, the therapeutic role of prostaglandin D₂ (PGD₂) was investigated on lipopolysaccharide (LPS)-induced lung injury in mice models and RAW264.7 macrophages through anti-inflammatory, histopathology, immunohistochemistry, and TUNEL staining. The overproduction of cytokines by RAW264.7 macrophages was observed after stimulation with LPS. However, pretreatment with PGD₂ decreased the production of cytokines. The level of inflammatory markers was significantly restored in the PGD₂ treatment group (TNF-α = 58.6 vs. 78.5 pg/mL; IL-1β = 29.3 vs. 36.6 pg/mL; IL-6 = 75.4 vs. 98.2 pg/mL; and CRP = 0.84 vs. 1.14 ng/mL). The wet/dry weight ratio of the lungs was quite significant in the disease control (LPS-only treatment) group. Moreover, the histological changes as determined by haematoxylin and eosin (H&E) staining clearly showed that PGD₂ treatment maintains the lung tissue architecture. The iNOS expression pattern was increased in lung tissues of LPS-treated animals, whereas, in mice treated with PGD₂, the expression of iNOS protein decreased. Flow cytometry data demonstrated that LPS intoxication enhanced apoptosis, which significantly decreased with PGD₂ treatment. In conclusion, all these observations indicate that PGD₂ provides an anti-inflammatory response in RAW264.7 macrophages and in ALI, and they suggest a therapeutic potential in lung pathogenesis.