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.