Bile-pancreatic juice exclusion increases p38MAPK activation and TNF-α production in ligation-induced acute pancreatitis in rats

Acute pancreatitis is associated with stress kinase activation and cytokine production. We hypothesize that bile-pancreatic juice exclusion activates p38(MAPK) and induces TNF-alpha production in ligation-induced acute pancreatitis. We compared rats with 1-3 h of duct ligation, duct ligation with duodenal bile-pancreatic juice replacement from a donor rat, and sham operation. Pancreatic homogenates were analyzed as follows: (a) Immunoblots using phospho-specific p38(MAPK) antibody showed increased p38(MAPK) activation after ligation that was inhibited by bile-pancreatic juice replacement. (b) Immune-complex kinase assay using ATF-2 as substrate showed increased p38(MAPK) activation after ligation that was subdued by bile-pancreatic juice replacement. (c) ELISA showed increased pancreatic TNF-alpha production after ligation that was significantly ameliorated by bile-pancreatic juice replacement.Bile-pancreatic juice exclusion from gut increases p38(MAPK) activation and TNF-alpha production in this experimental model. Our findings support our central hypothesis that bile-pancreatic juice exclusion exacerbates cell stress and acute inflammation in ligation-induced acute pancreatitis.