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Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis

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Journal of Gastrointestinal Surgery Aims and scope

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.

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Authors and Affiliations

  1. Department of Surgery, VAMC & University of Iowa Carver College of Medicine, 200 Hawkins Drive, 4625 JCP, 52242, Iowa City, IA

    Isaac Samuel M.D. (F.R.C.S., F.A.C.S., Assistant Professor)

  2. Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa

    Mark A. Yorek Ph.D.

  3. Department of Neurology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa

    Asgar Zaheer Ph.D.

  4. Department of Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa

    Rory A. Fisher Ph.D.

Authors
  1. Isaac Samuel M.D.
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  2. Mark A. Yorek Ph.D.
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  3. Asgar Zaheer Ph.D.
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  4. Rory A. Fisher Ph.D.
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Correspondence to Isaac Samuel M.D..

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Samuel, I., Yorek, M.A., Zaheer, A. et al. Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis. J Gastrointest Surg 10, 950–959 (2006). https://doi.org/10.1016/j.gassur.2006.04.007

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