Bile-pancreatic juice exclusion increases p38MAPK activation and TNF-alpha production in ligation-induced acute pancreatitis in rats.
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.


CONCLUSIONS
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.
Samuel
Isaac
I
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
Zaheer
Smita
S
Zaheer
Asgar
A
D000208:Acute Disease; D000818:Animals; D001646:Bile / Q000502:physiology*; D004789:Enzyme Activation; D015870:Gene Expression / Q000502:physiology*; D008026:Ligation; D008297:Male; D010189:Pancreatic Juice / Q000502:physiology*; D010195:Pancreatitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases