|Title||Experimental acute pancreatitis in PAP/HIP knock-out mice.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Gironella 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 Published||2007 Aug|
|Keywords||Acute 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.
|PubMed Central ID||PMC1955488|
|Grant List||G0000865 / / Medical Research Council / United Kingdom|