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

Background: The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/PAP cell stress genes (60-fold greater Reg3 alpha, and 10-fold greater PAP/Reg3 beta and Reg3 gamma). 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, Reg3a was strongly expressed in the untreated CF pancreas but not in wild type. During pancreatitis, Reg3a 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.