Background and aims: PAP/HIP was first reported as an additional pancreatic secretory protein expressed during the acute phase of pancreatitis. It was shown in vitro to be anti-apoptotic and anti-inflammatory. This study aims at looking whether PAP/HIP plays the same role in vivo.
Methods: A model of caerulein-induced pancreatitis was used to compare the outcome of pancreatitis in PAP/HIP-/- and wild-type mice.
Results: PAP/HIP-/- mice showed normal phenotype at birth and normal postnatal development. However, caerulein-induced pancreatic necrosis was less severe in PAP/HIP-/- mice than in wild-type, as judged by lower amylasemia and lipasemia and smaller areas of necrosis. On the contrary, pancreas from PAP/HIP-/- mice was more sensitive to apoptosis, in agreement with the anti- apoptotic effect of PAP/HIP in vitro. Surprisingly, pancreatic inflammation was more extensive in PAP/HIP-/- mice, as judged from histological parameters, increased myeloperoxidase activity and increased pro-inflammatory cytokine expression. This result, in apparent contradiction with the limited necrosis observed in these mice, is however in agreement with the anti- inflammatory function previously reported in vitro for PAP/HIP. This is supported by the observation that activation of the STAT3/SOCS3 pathway was strongly decreased in pancreas of PAP/HIP-/- mice and by the reversion of the apoptotic and inflammatory phenotypes upon administration of recombinant PAP/HIP to PAP/HIP-/- mice.
- pancrreatitis associated protein