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Experimental acute pancreatitis in PAP/HIP knock-out mice
  1. Meritxell Gironella
  1. INSERM U.624, France
    1. Emma Folch-Puy
    1. IIBB-CSIC, IDIBAPS, Spain
      1. Aude LeGoffic
      1. INSERM U.624, France
        1. Stéphane Garcia
        1. INSERM U.624, France
          1. Laurence Christa
          1. Laboratoire de Biochimie Métabolique, Hôpital Necker Enfants-Malades, France
            1. Andrew Smith
            1. Department of Anatomy and Developmental Biology, University College London, United Kingdom
              1. Luis Tebar
              1. Department of Anatomy and Developmental Biology, University College London, United Kingdom
                1. Stephen P Hunt
                1. Department of Anatomy and Developmental Biology, University College London, United Kingdom
                  1. Rosemary Bayne
                  1. Gene Targeting Laboratory, Institute for Stem Cell Research, University of Edinburgh, United Kingdom
                    1. Andrew JH Smith
                    1. Gene Targeting Laboratory, Institute for Stem Cell Research, University of Edinburgh, United Kingdom
                      1. Jean-Charles Dagorn
                      1. INSERM U.624, France
                        1. Daniel Closa
                        1. IIBB-CSIC, IDIBAPS, Spain
                          1. Juan L Iovanna (iovanna{at}marseille.inserm.fr)
                          1. INSERM U.624, France

                            Abstract

                            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.

                            • knock-out
                            • mice
                            • pancreas
                            • pancreatitis
                            • pancrreatitis associated protein

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