title: 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.affiliation: University of California Davis (College of Agricultureal and Environmental Sciences), Nutrition, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.affiliation: University of California Davis (College of Agricultureal and Environmental Sciences), Nutrition, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: University of California Davis (College of Agricultureal and Environmental Sciences), Nutrition, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Hammock
authors.affiliation: University of California Davis (College of Agricultureal and Environmental Sciences), Nutrition, USA.. Electronic address: fghaj@ucdavis.edu.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Haj