title: Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophages.
abstract: Rat peritoneal macrophages were stimulated with lipopolysaccaride (LPS) for various periods and their ability to convert exogenous arachidonic acid to various prostanoids was examined. Unstimulated cells, which expressed cyclooxygenase (COX)-1 but not COX-2, produced thromboxane (TX) B2 > prostaglandin (PG) D2 > PGE2, whereas cells stimulated for 6-12 h with LPS exhibited marked increase in conversion to PGE2, which paralleled COX-2 induction, with minimal change in conversion to TXB2 and PGD2. Pharmacological studies showed that formation of PGE2 was mediated predominantly by COX-2, PGD2 by COX-1, and TXB2 by both COX-1 and COX-2 depending upon the timing of LPS stimulation. Measurement of the conversion of exogenous PGH2 to each prostanoid in cell lysates demonstrated LPS-dependent increase in PGE2 synthase activity that was degenerated by pretreatment with actinomycin D or cycloheximide. Thus, concordant induction of terminal PGE2 synthase with COX-2 leads to the preferred production of PGE2 to TXB2 and PGD2 by LPS-stimulated macrophages.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Naraba
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: I
authors.initials: I
authors.lastname: Kudo
authors.forename: K
authors.initials: K
authors.lastname: Yamaki
authors.forename: A
authors.initials: A
authors.lastname: Ueno
authors.forename: S
authors.initials: S
authors.lastname: Oh-ishi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D007213:Indomethacin / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases; D007527:Isoenzymes / Q000096:biosynthesis*; D007535:Isomerases / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D003609:Dactinomycin; D013929:Thromboxane B2; D003513:Cycloheximide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin