First Author | Bettaieb A | Year | 2014 |
Journal | PLoS One | Volume | 9 |
Issue | 11 | Pages | e113019 |
PubMed ID | 25402489 | Mgi Jnum | J:225303 |
Mgi Id | MGI:5692367 | Doi | 10.1371/journal.pone.0113019 |
Citation | Bettaieb A, et al. (2014) Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice. PLoS One 9(11):e113019 |
abstractText | 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-kappaB 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. |