Nuclear factor-kB activation mediates inducible nitric oxide synthase expression in carrageenin-induced pleurisy.

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