Prostaglandin D2 receptor expression in the lung and the effect of PPAR-γ, DP1, and DP2 receptor agonist treatment during respiratory viral infection

Abstract

Abstract Prostaglandin D2 (PGD2) may play an anti-inflammatory role in the lung during respiratory viral infection, but little is known about the expression of its receptors (PPAR-γ, DP1, and DP2) in the lung or its mechanism of action. Adult C57BL/6 mice were infected with Sendai virus (500 pfu /g body weight), a natural mouse pathogen that infects airway epithelial cells. Immunostaining of uninfected lungs showed PPAR-γ protein in epithelial cells of larger airways, but not in the alveolar epithelial cells. After viral infection, PPAR-γ protein was no longer detectable in the lungs. Immunofluorescence showed DP1 present in parenchymal cells as well as in some CCSP+ airway epithelial cells, but levels did not appear to change during infection. DP2 expression increased after viral infection and was predominantly in CCSP+ epithelial cells 24 hours post-infection. DP2 also co-localized with MHC Class II+ cells in the parenchyma on days 3 and 7 post-infection. Viral infection of primary tracheal epithelial cells showed PPAR-γ mRNA expression was increased 48 and 72 hours post-infection. There was no change in DP1 or DP2 expression in vitro. To test the effect of each receptor in vivo, mice were infected and treated with PPAR-γ, DP1, and DP2 agonists, or vehicle every 12 hours. Mice treated with the PPAR-γ agonist were protected from body weight loss and had reduced IFN-γ expression on day 7, suggesting that PGD2 may be acting via PPAR-γ to reduce inflammation in the lung. Supported by grants from Sigma Xi Grant in Aid of Research and Saint Louis University College of Arts and Sciences Brennan Award.