title: Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression.
abstract: Injection of carrageenan 1% (50 microl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32-34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NO(x)) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E(2) levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX-2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX-2 expression at 6 and 24 h in 3-8-week-old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age-weight of mice, as opposite to COX-2 that is present only in the second phase of the oedema and is not linked to mouse age-weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX-1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX-1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age-weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX-1 and COX-2 in response to carrageenan injection in the two phases of the mouse paw oedema.
authors.affiliation: Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples-Federico II, via D. Montesano 49, Naples 80131, Italy.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Posadas
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Bucci
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Luca
authors.initials: L
authors.lastname: Parente
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D002351:Carrageenan / Q000633:toxicity; D051546:Cyclooxygenase 2; D004487:Edema / Q000139:chemically induced / Q000201:enzymology*; D005552:Forelimb / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases