Early NF-κB activation is associated with hormone-induced pancreatitis
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...
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Published in | American journal of physiology: Gastrointestinal and liver physiology Vol. 275; no. 6; pp. G1402 - G1414 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.1998
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0193-1857 1522-1547 |
DOI: | 10.1152/ajpgi.1998.275.6.G1402 |