Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice

被引:9
作者
Rossi, A
Cuzzocrea, S [1 ]
Mazzon, E
Serraino, I
De Sarro, A
Dugo, L
Felice, MR
Van de Loo, FAJ
Di Rosa, M
Musci, G
Caputi, AP
Sautebin, L
机构
[1] Univ Naples Federico II, Dept Expt Pharmacol, Naples, Italy
[2] Univ Messina, Sch Med, Inst Pharmacol, Torre Biol Policlin, I-98100 Messina, Italy
[3] Univ Messina, Sch Med, Dept Biomorphol, I-98100 Messina, Italy
[4] Univ Messina, Sch Med, Dept Organ & Biol Chem, I-98100 Messina, Italy
[5] Univ Nijmegen Hosp, Dept Rheumatol, Nijmegen, Netherlands
关键词
carrageenan; cyclooxygenase; inflammation; nitric oxide; prostaglandins;
D O I
10.1016/S0024-3205(02)02375-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 PGE(2) 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(1alpha) 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. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1199 / 1208
页数:10
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