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

Isaac Samuel; Mark A Yorek; Asgar Zaheer; Rory A Fisher

doi:10.1016/j.gassur.2006.04.007

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

Journal article

Peer reviewed

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

Isaac Samuel, Mark A Yorek, Asgar Zaheer and Rory A Fisher

Journal of gastrointestinal surgery, Vol.10(7), pp.950-959

07/2006

DOI: 10.1016/j.gassur.2006.04.007

PMID: 16843865

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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-kappaB (NF-kappaB) 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-kappaB (IkappaB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kappaB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkappaB, and NF-kappaB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kappaB 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-kappaB pathway activation and increases chemokine production in ligation-induced acute pancreatitis.

Phosphorylation

Immunoprecipitation

Chemokines - biosynthesis

Rats

Bile - metabolism

Immunoblotting

Male

NF-kappa B - metabolism

Rats, Sprague-Dawley

Animals

Chemokine CCL5 - biosynthesis

Ligation

Chemokine CCL2 - biosynthesis

Pancreatic Juice - metabolism

Electrophoretic Mobility Shift Assay

Pancreatitis - metabolism

Proto-Oncogene Proteins c-akt - metabolism

Disease Models, Animal

Details

Title: Subtitle: Bile-pancreatic juice exclusion promotes Akt/NF-kappaB activation and chemokine production in ligation-induced acute pancreatitis
Creators: Isaac Samuel - Department of Surgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA. Isaac-samuel@uiowa.edu
Mark A Yorek
Asgar Zaheer
Rory A Fisher
Resource Type: Journal article
Publication Details: Journal of gastrointestinal surgery, Vol.10(7), pp.950-959
Publisher: United States
DOI: 10.1016/j.gassur.2006.04.007
PMID: 16843865
ISSN: 1091-255X
eISSN: 1873-4626
Grant note: K08-DK062805 / NIDDK NIH HHS
Language: English
Date published: 07/2006
Academic Unit: Neurology; Iowa Neuroscience Institute; Surgery; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984040489702771

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