Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice

Ahmed Bettaieb, Samah Chahed, George Tabet, Jun Yang, Christophe Morisseau, Stephen M Griffey, Bruce D. Hammock, Fawaz Haj

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Methodology/Principal Findings: To investigate whether sEH may have a causal role in AP we utilized Ephx2 knockout (KO) mice to determine the effects of sEH deficiency on cerulein- and arginine-induced AP. sEH expression increased at the protein and messenger RNA levels, as well as enzymatic activity in the early phase of cerulein- and arginine-induced AP in mice. In addition, amylase and lipase levels were lower in cerulein-treated Ephx2 KO mice compared with controls. Moreover, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B and IL-6 were lower in ceruleintreated Ephx2 KO mice compared with controls. Further, Ephx2 KO mice exhibited decreased cerulein- and arginine-induced NF-kB inflammatory response, MAPKs activation and decreased cell death. Conclusions -These findings demonstrate a novel role for sEH in the progression of cerulein- and arginine-induced AP.

Background: Acute pancreatitis (AP) is a frequent gastrointestinal disorder that causes significant morbidity, and its incidence has been progressively increasing. AP starts as a local inflammation in the pancreas that often leads to systemic inflammatory response and complications. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory diseases, but its significance in AP remains unexplored.

Original languageEnglish (US)
Article numbere113019
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 17 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Bettaieb, A., Chahed, S., Tabet, G., Yang, J., Morisseau, C., Griffey, S. M., Hammock, B. D., & Haj, F. (2014). Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice. PLoS One, 9(11), [e113019]. https://doi.org/10.1371/journal.pone.0113019