Suyama Koichi, Ohmuraya Masaki, Hirota Masahiko, Ozaki Nobuyuki, Ida Satoshi, Endo Motoyoshi, Araki Kimi, Gotoh Tomomi, Baba Hideo, Yamamura Ken-Ichi
Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto, Japan.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):176-82. doi: 10.1016/j.bbrc.2007.12.132. Epub 2007 Dec 31.
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.
C/EBP同源蛋白（CHOP）是内质网应激途径中的主要介导因子之一。为了阐明内质网应激-CHOP途径在实验性胰腺炎中的作用，给野生型（Chop(+/+)）和Chop基因缺陷型（Chop(-/-)）小鼠注射蛙皮素（一种胆囊收缩素类似物），或同时注射蛙皮素和脂多糖（LPS）。在蛙皮素诱导的急性胰腺炎中，可诱导内质网应激、血清淀粉酶升高和组织学间质水肿。然而，无论CHOP是否存在，CHOP途径下游均无明显激活。而在蛙皮素和LPS模型中，与炎症相关的半胱天冬酶（半胱天冬酶-11、半胱天冬酶-1）和白细胞介素-1β被激活，但与凋亡相关的半胱天冬酶未被激活。在Chop(-/-)小鼠中，这些介质的表达水平恢复到基础水平，导致胰腺炎症状较轻，血清淀粉酶水平降低。这些结果表明，内质网应激-CHOP途径通过诱导与炎症相关的半胱天冬酶和白细胞介素-1β，在加速胰腺炎进程中起关键作用。
