Year: 2014
Type: article
Abstract: 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-κB 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.
Source: PLoS ONE
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1225459562, G1251846919, Role of adipose protein-tyrosine phosphatase 1B in glucose homeostasis and body m, G2366971526, Mouse Metabolic Phenotyping Center (MMPC) at UC Davis, West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC), G3068097868, Metabolic functions of adipose pyruvate kinase M2, Epoxyeicosanoids and Renal Vascular Function in Obesity & Hypertension, HYDROLYTIC ENZYMES IN THE METABOLISM OF TOXINS, G4227377382, G4578523318, G549601326, G622880495, Hydrolytic enzymes in the metabolism of toxins, Role of Protein-Tyrosine Phosphatase 1B in Pancreatic Islet Function, G7346897736, G761488926, G9000000914, G9000114809, G9000229097, G9000257392
OpenAlex ID: W1978627697