Soluble epoxide hydrolase deficiency ameliorates acute pancreatitis in mice.

Abstract

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

• Authors: Ahmed Bettaieb, Christophe Morisseau, Bruce Hammock, Fawaz Haj
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 75 Suppl 1 Pg. S32 (Oct 2014) ISSN: 1873-4596 [Electronic] United States
• PMID: 26461340 (Publication Type: Journal Article)
• Copyright: Copyright © 2014. Published by Elsevier Inc.