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Experimental acute pancreatitis in PAP/HIP knock-out mice.

TitleExperimental acute pancreatitis in PAP/HIP knock-out mice.
Publication TypeJournal Article
Year of Publication2007
AuthorsGironella M, Folch-Puy E, LeGoffic A, Garcia S, Christa L, Smith AG, Tebar L, Hunt SP, Bayne R, Smith AG, Dagorn J-C, Closa D, Iovanna JL
Date Published2007 Aug
KeywordsAcute Disease, Animals, Apoptosis, Autoantigens, Ceruletide, Disease Models, Animal, Lithostathine, Mice, Mice, Knockout, Necrosis, Pancreas, Pancreatitis, Phenotype, Proteins, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins

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.

Alternate JournalGut
PubMed ID17409121
PubMed Central IDPMC1955488
Grant ListG0000865 / / Medical Research Council / United Kingdom