Role of peroxisome proliferator-activated receptor-α in acute pancreatitis induced by cerulein

Tiziana Genovese, Emanuela Mazzon, Di Paola Rosanna, Carmelo Muià, Concetta Crisafulli, Giuseppe Malleo, Emanuela Esposito, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The peroxisome proliferator-activated receptor-α (PPAR-α) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid and thyroid hormone receptors. The aim of the present study was to examine the effects of endogenous PPAR-α ligand on the development of acute pancreatitis caused by cerulein in mice. Intraperitoneal injection of cerulein into PPAR-α wild-type (WT) mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and by elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as an increase in myeloperoxidase activity) was associated with enhanced expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) in the pancreas of cerulein-treated PPAR-α wild-type (WT) mice in comparison to sham-treated mice. Acute pancreatitis in PPAR-αWT mice was also associated with a significant mortality (20% survival at 5 days after cerulein administration). In contrast, the degree of pancreatic inflammation and tissue injury (histological score), up-regulation/ formation of ICAM-1 and P-selectin, infiltration of neutrophils, and the expression of TGF-β and VEGF was markedly enhanced in pancreatic tissue obtained from cerulein-treated PPAR-α knockout (KO) mice. Thus, endogenous PPAR-α ligands reduce the degree of pancreas injury caused by acute pancreatitis induced by cerulein administration.

Original languageEnglish
Pages (from-to)559-570
Number of pages12
JournalImmunology
Volume118
Issue number4
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Adhesion molecules
  • Inflammation
  • Neutrophil infiltration
  • Pancreatitis
  • PPAR-α

ASJC Scopus subject areas

  • Immunology

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    Genovese, T., Mazzon, E., Rosanna, D. P., Muià, C., Crisafulli, C., Malleo, G., Esposito, E., & Cuzzocrea, S. (2006). Role of peroxisome proliferator-activated receptor-α in acute pancreatitis induced by cerulein. Immunology, 118(4), 559-570. https://doi.org/10.1111/j.1365-2567.2006.02393.x