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

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.
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