Bile-Pancreatic Juice Exclusion Promotes Akt/NF-κB Activation and Chemokine Production in Ligation-Induced Acute Pancreatitis

Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice, obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice exclusion from gut exacerbates Akt/nuclear factor-κB (NF-κB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n = 7/group). Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-κB (IκB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-κB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IκB, and NF-κB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-κB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic juice replacement (ANOVA, P < 0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-κB pathway activation and increases chemokine production in ligation-induced acute pancreatitis.