C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis.
C/EBP homologous protein (CHOP) is one of the main mediating factors in the ER stress pathway. To elucidate the role of the ER stress-CHOP pathway in experimental pancreatitis, wild-type (Chop(+/+)) and Chop deficient (Chop(-/-)) mice were administered cerulein, a cholecystokinin analogue, or both cerulein and lipopolysaccharide (LPS). In cerulein-induced acute pancreatitis, ER stress, serum amylase elevation and histological interstitial edema were induced. However, there was no remarkable activation downstream of the CHOP pathway regardless of the presence or absence of CHOP. Whereas, in the cerulein and LPS model, inflammation-associated caspases (caspase-11, caspase-1) and IL-1beta, but not apoptosis-associated caspases, were activated. In Chop(-/-) mice, the expression levels of these mediators returned to basal levels resulting in a milder pancreatitis and decreased serum amylase level. These results indicated that the ER stress-CHOP pathway has a pivotal role in the acceleration of pancreatitis through the induction of inflammation-associated caspases and IL-1beta.
Suyama
Koichi
K
Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto, Japan.
Ohmuraya
Masaki
M
Hirota
Masahiko
M
Ozaki
Nobuyuki
N
Ida
Satoshi
S
Endo
Motoyoshi
M
Araki
Kimi
K
Gotoh
Tomomi
T
Baba
Hideo
H
Yamamura
Ken-Ichi
K
D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D015153:Blotting, Western; D002108:Ceruletide / Q000008:administration & dosage; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051742:Transcription Factor CHOP / Q000378:metabolism*
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051742:Transcription Factor CHOP; D002108:Ceruletide; D000681:Amylases