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

Abstract.

We studied the involvement of nuclear factor-κB (NF-κB) in the regulation of inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy. Injection of 0.2 ml of 1% λ-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 ΝF-κB/DNA binding activity. Treatment of rats with pyrrolidine dithiocarbamate (10, 30, and 100 mg/kg) and N-α-p-tosyl-l-lysine chloromethylketone (30 mg/kg), two inhibitors of NF-κB 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 ΝF-κB plays a key role in inducible NO synthase protein expression and in the development of inflammatory response.