Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice.

Abstract

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.

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 cerulein-treated Ephx2 KO mice compared with controls. Further, Ephx2 KO mice exhibited decreased cerulein- and arginine-induced NF-κB 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.

• Authors: Ahmed Bettaieb, Samah Chahed, George Tabet, Jun Yang, Christophe Morisseau, Stephen Griffey, Bruce D Hammock, Fawaz G Haj
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e113019 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25402489 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Ceruletide
• Epoxide Hydrolases

Topics

• Acute Disease
• Animals
• Cell Death (genetics)
• Ceruletide (adverse effects)
• Disease Models, Animal
• Epoxide Hydrolases (deficiency, genetics, metabolism)
• Gene Expression
• MAP Kinase Signaling System
• Male
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• Pancreatitis (chemically induced, enzymology, genetics, pathology)