Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair.
This investigation demonstrated a functional coupling between cyclooxygenase-1 (cox) and prostaglandin E2/D2 biosynthesis in murine skin repair. Cyclooxygenase-1 expression decreased transiently after excisional wounding, and this was followed by a marked fall in the rate of prostaglandin E2/D2 biosynthesis at the wound site. Expression of cyclooxygenase-1, prostaglandin synthases, and prostaglandin E2/D2 production were colocalized in new tissue at the margin of the wound. Although cyclooxygenase-2 expression was strongly induced in granulation tissue on injury, this isoform did not contribute to high prostaglandin E2/D2 concentrations in wounds. Accordingly, wound tissue from SC-560-treated mice (selective cyclooxygenase-1 inhibitor) and diclofenac-treated mice (nonselective cyclooxygenase inhibitor), but not celecoxib-treated mice (selective cyclooxygenase-2 inhibitor), and wound tissue from cyclooxygenase-1-deficient animals exhibited a severe loss of prostaglandin E2/D2 at the wound site, and this change was associated with an impairment in the normal wound morphology. Topically administered prostaglandin E2 (dinoprostone) was able to restore normal wound repair to diclofenac-treated mice. In contrast to the presence of an injury-induced cyclooxygenase-2, these data constitute strong evidence that cyclooxygenase-1-coupled prostaglandin E2/D2 biosynthesis has a central role in skin repair.
Kämpfer
Heiko
H
Pharmazentrum Frankfurt Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
Bräutigam
Lutz
L
Geisslinger
Gerd
G
Pfeilschifter
Josef
J
Frank
Stefan
S
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000493:pharmacokinetics; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D013058:Mass Spectrometry; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000493:pharmacokinetics; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D011720:Pyrazoles; C115461:SC 560; D004008:Diclofenac; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D012260:Ribonucleases; D015232:Dinoprostone; D015230:Prostaglandin D2