title: Experimental acute pancreatitis in PAP/HIP knock-out mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, U.624, Marseille, France.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Emma
authors.initials: E
authors.lastname: Folch-Puy
authors.forename: Aude
authors.initials: A
authors.lastname: LeGoffic
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.forename: Laurence
authors.initials: L
authors.lastname: Christa
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.forename: Luis
authors.initials: L
authors.lastname: Tebar
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunt
authors.forename: Rosemary
authors.initials: R
authors.lastname: Bayne
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Smith
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Dagorn
authors.forename: Daniel
authors.initials: D
authors.lastname: Closa
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000032:analysis; D002108:Ceruletide; D004195:Disease Models, Animal; D051847:Lithostathine / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000473:pathology*; D000073718:Pancreatitis-Associated Proteins; D010641:Phenotype; D011506:Proteins / Q000032:analysis*; D050796:STAT3 Transcription Factor / Q000032:analysis; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis
chemical_list: D001324:Autoantigens; D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C497615:Reg1 protein, mouse; C490253:Reg3b protein, mouse; C518252:RegII protein, mouse; C088549:RegIII protein, mouse; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D002108:Ceruletide