Isaac Samuel1, Smita Zaheer, Asgar Zaheer. 1. Department of Surgery, The University of Iowa, Roy J. and Lucille A. Carver College of Medicine and VAMC, 200 Hawkins Drive - 4625 JCP, Iowa City, IA 52242, USA. Isaac-samuel@uiowa.edu
Abstract
UNLABELLED: 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. CONCLUSION: 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. Copyright 2005 S. Karger AG, Basel and IAP
UNLABELLED: 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 donorrat, 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 pancreaticTNF-alpha production after ligation that was significantly ameliorated by bile-pancreatic juice replacement. CONCLUSION: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. Copyright 2005 S. Karger AG, Basel and IAP
Authors: Zuobiao Yuan; David K Meyerholz; Erik C Twait; Duraisamy Kempuraj; Deborah E Williard; Isaac Samuel Journal: J Gastrointest Surg Date: 2011-07-29 Impact factor: 3.452
Authors: Erwin J M van Geenen; Donald L van der Peet; Pranav Bhagirath; Chris J J Mulder; Marco J Bruno Journal: Nat Rev Gastroenterol Hepatol Date: 2010-08-10 Impact factor: 46.802