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

Abstract

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.