Bile-pancreatic juice exclusion promotes Akt/NF-kappaB activation and chemokine production in ligation-induced acute pancreatitis.
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.
Samuel
Isaac
I
Department of Surgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA. Isaac-samuel@uiowa.edu
Yorek
Mark A
MA
Zaheer
Asgar
A
Fisher
Rory A
RA
D000818:Animals; D001646:Bile / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D015151:Immunoblotting; D047468:Immunoprecipitation; D008026:Ligation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt