Sci. STKE, 3 May 2005
ALLERGIC RESPONSES Prostaglandin E2, a Negative Modulator
Although prostaglandins are produced during an allergic reaction and are generally considered to be mediators of inflammation, aspirin and other inhibitors of prostaglandin synthesis are ineffective in alleviating allergy symptoms. Genetic evidence indicates that prostaglandin D2 acting through the prostaglandin D receptor is involved in producing allergic symptoms. Kunikata et al. show that mice deficient in the prostaglandin E2 (PGE2) receptor EP3 (encoded by Ptger3) exhibited an exaggerated allergic asthma phenotype compared with wild-type mice or mice deficient in the other members of the EP family. An EP3 receptor agonist, AE-248, inhibited the allergic response of mice sensitized to ovalbumin, and this effect was absent in the Ptger3–/– mice. AE-248 or PGE2 also inhibited histamine and leukotriene release from cells cultured from ovalbumin-sensitized mice. In vivo, AE-248 administered 3 hours after antigen challenge inhibited allergic responses. Microarray analysis of cells from ovalbumin-sensitized mice treated with and without AE-248 showed that EP3 activation altered the genetic response to allergen, thus mediating a longer-term suppression of the allergic response. EP3 transcripts and protein were detected on the airway epithelial cells of sensitized mice. The authors suggest that PGE2 produced during allergic responses mediates an inhibitory effect by decreasing the secretion of inflammatory chemokines from airway epithelial cells expressing EP3.
T. Kunikata, H. Yamane, E. Segi, T. Matsuoka, Y. Sugimoto, S. Tanaka, H. Tanaka, H. Nagai, A. Ichikawa, S. Narumiya, Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat. Immunol. 6, 524-531 (2005). [PubMed]
Citation: Prostaglandin E2, a Negative Modulator. Sci. STKE 2005, tw164 (2005).
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