Experimental acute pancreatitis in PAP/HIP knock-out mice

Meritxell Gironella, Emma Folch-Puy, Aude LeGoffic, Stéphane Garcia, Laurence Christa, Andrew Smith, Luis Tebar, Stephen P. Hunt, Rosemary Bayne, Andrew J H Smith, Jean Charles Dagorn, Daniel Closa, Juan L. Iovanna*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 to look at 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 the normal phenotype at birth and normal postnatal development. Caerulein-induced pancreatic necrosis was, however, less severe in PAP/HIP -/- mice than in wild-type mice, as judged by lower amylasemia and lipasemia levels 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 the 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. Conclusion: The anti-apoptotic and anti-inflammatory functions described in vitro for PAP/HIP have physiological relevance in the pancreas in vivo during caerulein-induced pancreatitis.

Original languageEnglish
Pages (from-to)1091-1097
Number of pages7
Issue number8
Publication statusPublished - 1 Aug 2007


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