Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice.
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.
Rossi
Antonietta
A
Department of Experimental Pharmacology, University Federico II, Naples, Italy.
Cuzzocrea
Salvatore
S
Mazzon
Emanuela
E
Serraino
Ivana
I
De Sarro
Angela
A
Dugo
Laura
L
Felice
Maria Rosa
MR
Van de Loo
Fons A J
FA
Di Rosa
Massimo
M
Musci
Giovanni
G
Caputi
Achille P
AP
Sautebin
Lidia
L
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
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