Abstract
BackgroundThe 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.MethodsTo 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.ResultsIn 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.ConclusionThese 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.
Highlights
The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/pancreatitis associated protein (PAP) cell stress genes (60-fold greater Reg3α, and 10-fold greater PAP/Reg3β and Reg3γ)
To test whether constitutive elevation of Reg/PAP genes in the CF mouse pancreas affects the severity of acute pancreatitis, the caerulein supramaximal stimulation model was used [30]
There was slightly less serum amylase activity in CF mice compared to wild type after a single caerulein injection and at 7 h and 12 h after the complete series of caerulein injections (Fig. 1A) which may be related to the decreased tissue content of digestive enzymes in the CF mouse pancreas
Summary
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. There is a strong association of the Reg/PAP genes with pancreatic stress and injury, especially in response to pancreatitis [1,2]. The role of these proteins has been investigated under various conditions. The anti-apoptotic activity of Reg/PAP is of interest to pancreatitis, as experimental evidence shows that reduction of apoptosis can be associated with a worsened severity of pancreatitis [8,9]
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