Early NF-κB activation is associated with hormone-induced pancreatitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 275; no. 6; pp. G1402 - G1414
• Main Authors: Gukovsky, Ilya, Gukovskaya, Anna S, Blinman, Thane A, Zaninovic, Vjekoslav, Pandol, Stephen J
• Format: Journal Article
• Language: English
• Published: United States 01.12.1998
• Subjects: IκB; pancreatic acinar cell; KC; interleukin-6
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.1998.275.6.G1402

Inflammation and cell death are critical to pathogenesis of acute pancreatitis. Here we show that transcription factor nuclear factor-κB (NF-κB), which regulates these processes, is activated and plays a role in rat cerulein pancreatitis. NF-κB was strongly activated in the pancreas within 30 min of cerulein infusion; a second phase of NF-κB activation was prominent at 3-6 h. This biphasic kinetics could result from observed transient degradation of the inhibitory protein IκBα and slower but sustained degradation of IκBβ. The hormone also caused NF-κB translocation and IκB degradation in vitro in dispersed pancreatic acini. Both p65/p50 and p50/p50, but not c-Rel, NF-κB complexes were manifest in pancreatitis and in isolated acini. Coinfusion of CCK JMV-180, which abolishes pancreatitis, prevented cerulein-induced NF-κB activation. The second but not early phase of NF-κB activation was inhibited by a neutralizing tumor necrosis factor-α antibody. Antioxidant N-acetylcysteine (NAC) blocked NF-κB activation and significantly improved parameters of pancreatitis. In particular, NAC inhibited intrapancreatic trypsin activation and mRNA expression of cytokines interleukin-6 and KC, which were dramatically induced by cerulein. The results suggest that NF-κB activation is an important early event that may contribute to inflammatory and cell death responses in acute pancreatitis.