Enteral exclusion increases MAP kinase activation and cytokine production in a model of gallstone pancreatitis.
BACKGROUND
We have previously demonstrated that enteral exclusion augments pancreatic p38 mitogen-activated protein (MAP) kinase activation and tumor necrosis factor-alpha (TNF-alpha) production after bile-pancreatic duct ligation in rats.


METHODS
In the present study, we evaluated c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activation, and cytokine production, in pancreata of duct-ligated rats with and without duodenal bile-pancreatic juice replacement from a donor rat. We hypothesized that enteral exclusion of bile-pancreatic juice activates stress kinases and induces cytokine production in ligation-induced acute pancreatitis.


RESULTS
Increased JNK and ERK activation after ligation are inhibited by bile-pancreatic juice replacement. Increases in pancreatic production of IL-1beta and IL-12 after ligation are significantly subdued by replacement. In additional in vitro studies, we show that cholecystokinin- or TNF-alpha-stimulated nuclear transcription factor kappa-B activation in AR42J cells is inhibited by dominant negative ERK2.


CONCLUSIONS
Our novel findings using our Donor Rat Model indicate that bile-pancreatic juice exclusion induces MAP kinase activation and exacerbates cell stress and inflammation in this experimental model of gallstone pancreatitis. and IAP.
Samuel
Isaac
I
Department of Surgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa, USA. isaac-samuel@uiowa.edu
Tephly
Linda
L
Williard
Deborah E
DE
Carter
A Brent
AB
D000818:Animals; D001646:Bile / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D042882:Gallstones / Q000150:complications*; D005786:Gene Expression Regulation; D007249:Inflammation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010189:Pancreatic Juice / Q000378:metabolism; D010195:Pancreatitis / Q000097:blood / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D020928:Mitogen-Activated Protein Kinases