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


RESULTS
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.
Department of Nutrition, University of California Davis, Davis, California, United States of America.
Ahmed
A
Bettaieb
Department of Nutrition, University of California Davis, Davis, California, United States of America.
Samah
S
Chahed
Department of Nutrition, University of California Davis, Davis, California, United States of America.
George
G
Tabet
Department of Entomology and Nematology, University of California Davis, Davis, California, United States of America; Comprehensive Cancer Center, University of California Davis, Sacramento, California, United States of America.
Jun
J
Yang
Department of Entomology and Nematology, University of California Davis, Davis, California, United States of America; Comprehensive Cancer Center, University of California Davis, Sacramento, California, United States of America.
Christophe
C
Morisseau
Comparative Pathology Laboratory, University of California Davis, Davis, California, United States of America.
Stephen
S
Griffey
Department of Entomology and Nematology, University of California Davis, Davis, California, United States of America; Comprehensive Cancer Center, University of California Davis, Sacramento, California, United States of America.
Bruce D
BD
Hammock
Department of Nutrition, University of California Davis, Davis, California, United States of America; Comprehensive Cancer Center, University of California Davis, Sacramento, California, United States of America; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of California Davis, Sacramento, California, United States of America.
Fawaz G
FG
Haj
D000208:Acute Disease; D000818:Animals; D016923:Cell Death / Q000235:genetics; D002108:Ceruletide / Q000009:adverse effects; D004195:Disease Models, Animal; D004851:Epoxide Hydrolases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D016328:NF-kappa B; D002108:Ceruletide; D004851:Epoxide Hydrolases