Nuclear factor-kappaB activation mediates inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy

Naunyn Schmiedebergs Arch Pharmacol. 1999 Dec;360(6):670-5. doi: 10.1007/s002109900149.

Abstract

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.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Carrageenan
  • Cell Movement / drug effects
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Exudates and Transudates / cytology
  • Exudates and Transudates / drug effects
  • Leukocyte Count / drug effects
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / drug effects
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Nitrates / metabolism
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Pleural Effusion / chemically induced
  • Pleural Effusion / cytology
  • Pleurisy / chemically induced
  • Pleurisy / enzymology*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Wistar
  • Serine Proteinase Inhibitors / pharmacology
  • Thiocarbamates / pharmacology
  • Tosyllysine Chloromethyl Ketone / pharmacology
  • Transcription Factor RelA

Substances

  • Antioxidants
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nitrates
  • Nitrites
  • Pyrrolidines
  • Serine Proteinase Inhibitors
  • Thiocarbamates
  • Transcription Factor RelA
  • Tosyllysine Chloromethyl Ketone
  • pyrrolidine dithiocarbamic acid
  • Carrageenan
  • DNA
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat