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 DP 1 receptor in nasal obstruction using animals sensitized with ovalbumin in the presence of adjuvant, the contribution of the DP 1 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 DP 1 receptor antagonists suppressed JC pollen extract-induced sneezing and that a DP 1 receptor agonist induced sneezing. Moreover, JC pollen extract-induced sneezing was diminished in DP 1 receptor knockout mice. In conclusion, we developed a novel mouse model of allergic rhinitis that closely mimics human JC pollinosis. A strong contribution of DP 1 receptor signaling to sneezing was demonstrated using this model, suggesting that DP 1 receptor antagonists could suppress sneezing and nasal obstruction, and therefore these agents could be a new therapeutic option for allergic rhinitis.

Prostaglandins in asthma and allergic diseases

“…While DP 1 agonist increased allergen-induced sneezing compared to placebo in a model of Japanese cedar pollen-induced allergic rhinitis, this endpoint was reduced in DP 1 knockout mice compared to WT mice. (Nakano et al, 2016) These investigators also reported a DP 1 antagonist completely inhibited PGD 2 -induced augmentation of electrical and histamine-induced excitability of trigeminal ganglion excitability in guinea pigs. (Nagira et al, 2016) Allergen sensitized and challenged DP 1 KO mice had significantly inhibited airway responsiveness and BAL concentrations of IL-4, IL-5, and IL-13 compared to WT mice, while there was no difference in the BAL levels of IFN-γ.…”

Animal model of allergy and asthma; protocol for researches

“…In modeling, 10 µl of 3 mg/ml pollen extract in PBS is intranasally administered on days 0 and this is repeated on day 7,14,21,22,23,24,27,28,29, and 30 ( Figure 7). Pollen extract Administration should be done without anesthesia to stop pollen extract reaching to the lower airways (64)(65)(66)(67). Administration methods are shown in Figure 8.…”

Regulation of inflammation by lipid mediators in oral diseases

“…However, PGD 2 is most known for its pro-inflammatory properties in a variety of pathologies. Notably, it exacerbates adjuvant induced joint inflammation (Tsubosaka et al, 2014), allergic rhinitis (Nakano et al, 2016), Crohn's disease (Le Loupp et al, 2015;Radnai et al, 2016), and mast cell-induced vitreoretinopathy (Kuo et al, 2015). It also plays a role in depression-related behavior (Onaka et al, 2015) and in pain, being implicated in esophageal nociception (Zhang et al, 2013a), migraine (Antonova et al, 2013), and neuropathic spinal pain (Kanda et al, 2013).…”