Prostaglandin E2 receptor EP2, EP3, and EP4 agonists inhibit antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats.
OBJECTIVE
Prostaglandin (PG) E2 is a potential anti-inflammatory mediator that attenuates airway inflammation. To elucidate the functions of the PGE2 receptors (EP1, EP2, EP3, and EP4) in allergic inflammation, we examined the in vivo effects of EP agonists on mucus hypersecretion and eosinophil infiltration in rat nasal epithelium.


METHODS
We induced hypertrophic and metaplastic changes in goblet cells in nasal epithelium of ovalbumin-sensitized rats by intranasal challenge with ovalbumin. The effects of subcutaneous injections of EP agonists on mucus production and eosinophil infiltration were examined.


RESULTS
The EP4 agonist (1 to 100 microg/kg) dose-dependently inhibited ovalbumin-induced mucus production. The EP2 and EP3 agonists (100 microg/kg) also significantly inhibited mucus production. The EP3 agonist inhibited antigen-induced eosinophil infiltration, whereas the EP1 agonist showed no effect. This suppression of mucus production by the EP4 agonist was only effective when the EP4 agonist was given in the effector phase; administration in the induction phase resulted in no effect.


CONCLUSIONS
These results indicate that PGE2 acts as an anti-inflammatory mediator via the EP receptors of airways in allergic inflammation. Selective EP agonists may provide a new therapeutic strategy for airway mucus hypersecretion.
Hattori
Reiko
R
Department of Otorhinolaryngology--Head and Neck Surgery, Mie University School of Medicine, Tsu, Japan.
Shimizu
Shino
S
Majima
Yuichi
Y
Shimizu
Takeshi
T
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000209:etiology; D008297:Male; D008679:Metaplasia / Q000209:etiology; D008738:Methyl Ethers / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000502:physiology; D012220:Rhinitis / Q000209:etiology* / Q000473:pathology
C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D008738:Methyl Ethers; C121546:ONO AE 248; C461399:ONO-AE1-329; C500045:ONO-DI-004; D018078:Receptors, Prostaglandin E; D000527:Alprostadil; D015232:Dinoprostone