Department of Medicine, Division of Gastroenterology
Animals; Antigens, Neoplasm; Caerulein; Disease Models, Animal; Female; *Gene Expression Regulation; Lectins, C-Type; Male; Mice; Mice, Inbred CFTR; Pancreas; Pancreatitis; Peroxidase; Proteins; RNA; Regeneration; Tumor Markers, Biological
Gastroenterology | Life Sciences | Medicine and Health Sciences
BACKGROUND: The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/PAP cell stress genes (60-fold greater Reg3alpha, and 10-fold greater PAP/Reg3beta and Reg3gamma). These genes are suggested to be involved in protection or recovery from pancreatic injury.
METHODS: To test this idea the supramaximal caerulein model was used to induce acute pancreatitis in wild type and CF mice. Serum amylase, pancreatic water content (as a measure of edema), pancreatic myeloperoxidase activity, and Reg/PAP expression were quantified.
RESULTS: In both wild type and CF mice caerulein induced similar elevations in serum amylase (maximal at 12 h), pancreatic edema (maximal at 7 h), and pancreatic myeloperoxidase activity (MPO, a marker of neutrophil infiltration; maximal at 7 h). By immunohistochemistry, Reg3alpha was strongly expressed in the untreated CF pancreas but not in wild type. During pancreatitis, Reg3alpha was intensely expressed in foci of inflamed tissue in both wild type and CF.
CONCLUSION: These data demonstrate that the severity of caerulein-induced pancreatitis is not ameliorated in the CF mouse even though the Reg/PAP stress genes are already highly upregulated. While Reg/PAP may be protective they may also have a negative effect during pancreatitis due to their anti-apoptotic activity, which has been shown to increase the severity of pancreatitis.
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© 2006 Norkina et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
BMC Gastroenterol. 2006 May 15;6:16. Link to article on publisher's site
Norkina, Oxana; Graf, Rolf; Appenzeller, Philippe; and De Lisle, Robert C., "Caerulein-induced Acute Pancreatitis in Mice that Constitutively Overexpress Reg/PAP Genes" (2006). Open Access Articles. 2280.