Gironella, M and Folch-Puy, E and LeGoffic, A and Garcia, S and Christa, L and Smith, A and Tebar, L and Hunt, SP and Bayne, R and Smith, AJH and Dagorn, JC and Closa, D and Iovanna, JL (2007) Experimental acute pancreatitis in PAP/HIP knock-out mice. GUT , 56 (8) 1091 - 1097. 10.1136/gut.2006.116087.
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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.
|Title:||Experimental acute pancreatitis in PAP/HIP knock-out mice|
|Keywords:||PROTEIN-I, LIVER-REGENERATION, SECRETORY PROTEIN, ACINAR-CELLS, PAP-I, EXPRESSION, APOPTOSIS, GENE, INDUCTION, SEVERITY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
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