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Open Access Research article

Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes

Oxana Norkina1, Rolf Graf2, Philippe Appenzeller2 and Robert C De Lisle1*

Author Affiliations

1 Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas, USA

2 Pancreatitis Research Laboratory, Division of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland

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BMC Gastroenterology 2006, 6:16  doi:10.1186/1471-230X-6-16

Published: 15 May 2006

Abstract

Background

The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/PAP cell stress genes (60-fold greater Reg3α, and 10-fold greater PAP/Reg3β and Reg3γ). 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, Reg3α was strongly expressed in the untreated CF pancreas but not in wild type. During pancreatitis, Reg3α 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.