Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3.
Prostaglandins, including PGD(2) and PGE(2), are produced during allergic reactions. Although PGD(2) is an important mediator of allergic responses, aspirin-like drugs that inhibit prostaglandin synthesis are generally ineffective in allergic disorders, suggesting that another prostaglandin-mediated pathway prevents the development of allergic reactions. Here we show that such a pathway may be mediated by PGE(2) acting at the prostaglandin E receptor EP3. Mice lacking EP3 developed allergic inflammation that was much more pronounced than that in wild-type mice or mice deficient in other prostaglandin E receptor subtypes. Conversely, an EP3-selective agonist suppressed the inflammation. This suppression was effective when the agonist was administered 3 h after antigen challenge and was associated with inhibition of allergy-related gene expression. Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions.
Kunikata
Tomonori
T
Department of Pharmacology and Faculty of Medicine and Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Yamane
Hana
H
Segi
Eri
E
Matsuoka
Toshiyuki
T
Sugimoto
Yukihiko
Y
Tanaka
Satoshi
S
Tanaka
Hiroyuki
H
Nagai
Hiroichi
H
Ichikawa
Atsushi
A
Narumiya
Shuh
S
D000485:Allergens / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000819:agonists; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype
D000485:Allergens; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015232:Dinoprostone