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Enteral Exclusion Increases Map Kinase Activation and Cytokine Production in a Model of Gallstone Pancreatitis
Journal article   Open access   Peer reviewed

Enteral Exclusion Increases Map Kinase Activation and Cytokine Production in a Model of Gallstone Pancreatitis

Isaac Samuel, Linda Tephly, Deborah E Williard and A. Brent Carter
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Vol.8(1), pp.6-14
04/2008
DOI: 10.1159/000114850
PMCID: PMC2829292
PMID: 18235211
url
https://europepmc.org/articles/pmc2829292View
Published (Version of record) Open Access

Abstract

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.
c-Jun NH2-terminal kinase Acute pancreatitis Rapid Communication Cytokine Extracellular signal-regulated kinase Stress-activated protein kinase Cholecystokinin Acinar cell Donor Rat Model

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