Nuclear factor-kappaB activation mediates inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy.
We studied the involvement of nuclear factor-kappaB (NF-kappaB) in the regulation of inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy. Injection of 0.2 ml of 1% lambda-carrageenin into the pleural cavity of male Wistar rats caused after 6 h: (a) exudate formation and leukocyte migration into the pleural cavity; (b) inducible NO synthase protein expression and accumulation of NO2- plus NO3- in pleural exudate; (c) increase in p50/p65 nuclear level as well as NF-kappaB/DNA binding activity. Treatment of rats with pyrrolidine dithiocarbamate (10, 30, and 100 mg/kg) and N-alpha-p-tosyl-L-lysine chloromethylketone (30 mg/kg), two inhibitors of NF-kappaB activation, given subcutaneously concomitantly with carrageenin, caused a significant inhibition of all the parameters assayed. These results suggest that in carrageenin-induced rat pleurisy the activation of NF-kappaB plays a key role in inducible NO synthase protein expression and in the development of inflammatory response.
D'Acquisto
F
F
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Ialenti
A
A
Ianaro
A
A
Carnuccio
R
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005122:Exudates and Transudates / Q000166:cytology / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010996:Pleural Effusion / Q000139:chemically induced / Q000166:cytology; D010998:Pleurisy / Q000139:chemically induced / Q000201:enzymology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D051996:Transcription Factor RelA
D000975:Antioxidants; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009566:Nitrates; D009573:Nitrites; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D014107:Tosyllysine Chloromethyl Ketone; C020972:pyrrolidine dithiocarbamic acid; D002351:Carrageenan; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat