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 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.


CONCLUSIONS
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.
Norkina
Oxana
O
Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas, USA. Oxana.Norkina@umassmed.edu
Graf
Rolf
R
Appenzeller
Philippe
P
De Lisle
Robert C
RC
D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012038:Regeneration
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse; D012313:RNA; D002108:Ceruletide; D009195:Peroxidase