title: E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2 in acute cutaneous inflammation.
abstract: PGs are derived from arachidonic acid by PG-endoperoxide synthase (PTGS)-1 and PTGS2. Although enhanced levels of PGs are present during acute and chronic inflammation, a functional role for prostanoids in inflammation has not been clearly defined. Using a series of genetically engineered mice, we find that PTGS1 has the capacity to induce acute inflammation, but PTGS2 has negligible effects on the initiation of this response. Furthermore, we show that the contribution of PTGS1 is mediated by PGE(2) acting through the E-prostanoid (EP)3 receptor. Moreover, in the absence of EP3 receptors, inflammation is markedly attenuated, and the addition of nonsteroidal anti-inflammatory agents does not further impair the response. These studies demonstrate that PGE(2) promotes acute inflammation by activating EP3 receptors and suggest that EP3 receptors may be useful targets for anti-inflammatory therapy.
authors.affiliation: Division of Nephrology, Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goulet
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Pace
authors.forename: Mikelle L
authors.initials: ML
authors.lastname: Key
authors.forename: Robert S
authors.initials: RS
authors.lastname: Byrum
authors.forename: MyTrang
authors.initials: M
authors.lastname: Nguyen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
authors.forename: Scott G
authors.initials: SG
authors.lastname: Morham
authors.forename: Robert
authors.initials: R
authors.lastname: Langenbach
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Stock
authors.forename: John D
authors.initials: JD
authors.lastname: McNeish
authors.forename: Oliver
authors.initials: O
authors.lastname: Smithies
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000235:genetics; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D018078:Receptors, Prostaglandin E; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin