Role of prostaglandin D2 and DP1 receptor on Japanese cedar pollen-induced allergic rhinitis in mice

Abstract

Although we previously demonstrated the contribution of the DP1 receptor in nasal obstruction using animals sensitized with ovalbumin in the presence of adjuvant, the contribution of the DP1 receptor in sneezing is unclear. Here, we developed a mouse model of Japanese cedar (JC: Cryptomeria japonica) pollinosis to evaluate the symptoms of sneezing. To achieve this, we used JC pollen crude extract in the absence of adjuvant to sensitize mice to develop a model closer to the pathophysiology of human JC pollinosis. The immunologic and pharmacologic features of this model are highly similar to those observed in JC pollinosis in humans. Using this model, we found that DP1 receptor antagonists suppressed JC pollen extract-induced sneezing and that a DP1 receptor agonist induced sneezing. Moreover, JC pollen extract-induced sneezing was diminished in DP1 receptor knockout mice. In conclusion, we developed a novel mouse model of allergic rhinitis that closely mimics human JC pollinosis. A strong contribution of DP1 receptor signaling to sneezing was demonstrated using this model, suggesting that DP1 receptor antagonists could suppress sneezing and nasal obstruction, and therefore these agents could be a new therapeutic option for allergic rhinitis.