title: Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice.
abstract: In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory response in iNOSKO mice was significantly reduced in respect to iNOSWT animals, as demonstrated by the exudate volume (-63%) and numbers of infiltrating cells (-62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were significantly (p < 0.01) decreased in iNOSKO mice (16 +/- 7.6 nmoles/mice) compared to iNOSWT animals (133 +/- 9 nmoles/mice). Similarly, the amounts of PGE2 in the pleural exudates of carrageenan-treated animals were significantly (p < 0.01) lower in iNOSKO compared to iNOSWT mice (120 +/- 20 pg/mice vs. 308 +/- 51 pg/mice). Also the amounts of 6-keto-PGF(1 alpha) produced by lungs from carrageenan-treated iNOSKO mice (1.01 +/- 0.10 ng/tissue mg) were significantly (p < 0.01) reduced compared to iNOSWT carrageenan-treated mice (2.1 +/- 0.09 ng/tissue mg). In conclusion our results confirm, by the use of iNOSKO mice that in carrageenan-induced pleurisy NO positively modulates PG biosynthesis.
authors.affiliation: Department of Experimental Pharmacology, University Federico II, Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Angela
authors.initials: A
authors.lastname: De Sarro
authors.forename: Laura
authors.initials: L
authors.lastname: Dugo
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Felice
authors.forename: Fons A J
authors.initials: FA
authors.lastname: Van de Loo
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Rosa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musci
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002351:Carrageenan; D002452:Cell Count; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D005122:Exudates and Transudates / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007527:Isoenzymes; D011453:Prostaglandins; D012333:RNA, Messenger; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone