Inflammation and cell death are critical to pathogenesis of acute pancreati
tis. Here we show that transcription factor nuclear factor-kappa B (NF-kapp
a B), which regulates these processes, is activated and plays a role in rat
cerulein pancreatitis. NF-kappa B was strongly activated in the pancreas w
ithin 30 min of cerulein infusion; a second phase of NF-kappa B activation
was prominent at 3-6 h. This biphasic kinetics could result from observed t
ransient degradation of the inhibitory protein I kappa B alpha and slower b
ut sustained degradation of I kappa B beta. The hormone also caused NF-kapp
a B translocation and I kappa B degradation in vitro in dispersed pancreati
c acini. Both p65/p50 and p50/p50, but not c-Rel, NF-kappa B complexes were
manifest in pancreatitis and in isolated acini. Coinfusion of CCK JMV-180,
which abolishes pancreatitis, prevented cerulein-induced NF-kappa B activa
tion. The second but not early phase of NF-kappa B activation was inhibited
by a neutralizing tumor necrosis factor-alpha antibody. Antioxidant N-acet
ylcysteine (NAC) blocked NF-kappa B activation and significantly improved p
arameters of pancreatitis. In particular, NAC inhibited intrapancreatic try
psin activation and mRNA expression of cytokines interleukin-6 and KC, whic
h were dramatically induced by cerulein. The results suggest that NF-kappa
B activation is an important early event that may contribute to inflammator
y and cell death responses in acute pancreatitis.