E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2 in acute cutaneous inflammation.
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.
Goulet
Jennifer L
JL
Division of Nephrology, Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA.
Pace
Amy J
AJ
Key
Mikelle L
ML
Byrum
Robert S
RS
Nguyen
MyTrang
M
Tilley
Stephen L
SL
Morham
Scott G
SG
Langenbach
Robert
R
Stock
Jeffrey L
JL
McNeish
John D
JD
Smithies
Oliver
O
Coffman
Thomas M
TM
Koller
Beverly H
BH
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
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