C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis
C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis
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DOI：
10.1016/j.bbrc.2007.12.132
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发表时间：
2008-02-29
影响因子：
3.1
通讯作者：
Yamamura, Ken-ichi
中科院分区：
文献类型：
--
作者：
Suyama, Koichi;Ohmuraya, Masaki;Yamamura, Ken-ichi
C/EBP同源蛋白（CHOP）是内质网应激途径的主要介导因子之一。为了阐明内质网应激- Chop通路在实验性胰腺炎中的作用，我们给野生型（Chop(+/+)）和Chop缺陷型（Chop(-/-)）小鼠注射了蓝蛋白、胆囊收缩素类似物或蓝蛋白和脂多糖（LPS）。蛋白诱导的急性胰腺炎可引起内质网应激、血清淀粉酶升高和组织学间质水肿。然而，无论CHOP存在与否，CHOP通路的下游都没有明显的激活。然而，在cerulein和LPS模型中，炎症相关的半胱天冬酶（caspase-11, caspase-1）和IL-1 β被激活，而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，导致较轻的胰腺炎和血清淀粉酶水平降低。这些结果表明内质网应激- chop通路通过诱导炎症相关的半胱天冬酶和IL- I β在胰腺炎加速中起关键作用。(C) 2007爱思唯尔公司版权所有。
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-1 beta, 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- I beta. (C) 2007 Elsevier Inc. All rights reserved.