Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 174, Issue 5, Pages 1786-1798Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.080864
Keywords
-
Categories
Funding
- Ministry of Health, Labor, and Welfare of Japan
- Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
Ask authors/readers for more resources
Although recent reports suggest that the endoplasm ic reticulum (ER) stress response is induced in association with the development of inflammatory bowel disease, its role in the pathogenesis of inflammatory bowel disease remains unclear. The CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a transcription factor that is involved in the ER stress response, especially ER stress-induced apoptosis. In this study, we found that experimental colitis was ameliorated in CHOP-null mice, suggesting that CHOP exacerbates the development of colitis. The mRNA expression of Mac-1 (CD11b, a positive regulator of macrophage infiltration), Ero-1 alpha, and Caspase-11 (a positive regulator of interleukin-1 beta production) in the intestine was induced with the development of colitis, and this induction was suppressed in CHOP-null mice. ERO-1 alpha is involved in the production of reactive oxygen species (ROS); an increase in ROS production, which is associated with the development of colitis in the intestine, was suppressed in CHOP-null mice. A greater number of apoptotic cells in the intestinal mucosa of wild-type mice were observed to accompany the development of colitis compared with CHOP-null mice, suggesting that up-regulation of CHOP expression exacerbates the development of colitis. Furthermore, this CHOP activity appears to involve various stimulatory mechanisms, such as macrophage infiltration via the induction of Mac-1, ROS production via the induction of ERO-1 alpha, interleukin-1 beta production via the induction of Caspase-11, and intestinal mucosal cell apoptosis. (Am J Patbol 2009, 174.4786-1796 DOI. 10.2353/ajpath.2009.080864)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available