Signal enhancement of D prostanoid receptor prevents the development of food allergy

[Speaker] Tatsuro Nakamura:1
[Co-author] Rina Hirai:1, Takahisa Murata:1
1:Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

Oral food antigen-induced allergic reactions largely depend on the activation of the intestinal mast cells. Previously we demonstrated that endogenous prostaglandin D2 (PGD2) acts as a negative regulator of food allergy and anaphylaxis through D prostanoid (DP) receptor. Here, we investigate whether the signal enhancement of DP exerts a preventive and/or therapeutic effect on the development of food allergy. Food allergy model was generated by repeated oral challenges of ovalbumin (OVA) in BALB/c wild type (WT) mice. To examine the preventive or therapeutic effect of DP activation, WT mice were pre- or post-treated with a specific DP receptor agonist, BW245C (100 μg/kg, i.p., three times per day) during OVA challenges. OVA induced representative allergic responses diarrhea, accompanied by intestinal mast cell expansion in the vehicle (2% DMSO)-treated mice. Pre-treatment with DP agonist almost completely suppressed the induction of diarrhea and strongly inhibited the mast cell expansion. The mRNA expression of a chemoattractant of mast cells, CCL-2, was strongly inhibited in the DP agonist-treated mice intestine. Post-treatment with DP agonist also reduced the severity of allergic symptoms by decreasing the number of intestinal mast cells. In addition, impaired degranulation of mast cells was observed in the DP agonist-treated mice intestine. Taken together, signal enhancement of DP receptor exerts preventive and therapeutic effects on the development of food allergy in mice.
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