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Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis
Authors:Isaac Samuel M.D.  Mark A. Yorek Ph.D.  Asgar Zaheer Ph.D.  Rory A. Fisher Ph.D.
Affiliation:(1) Department of Surgery, VAMC & University of Iowa Carver College of Medicine, 200 Hawkins Drive, 4625 JCP, 52242 Iowa City, IA;(2) Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa;(3) Department of Neurology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa;(4) Department of Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa
Abstract: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-kB (NF-kB) 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-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB 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-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis. Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).
Keywords:Acute pancreatitis  Akt  NF-kB  chemokines  bile
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