RRC ID 67948
Author Namba T, Tanaka K, Ito Y, Ishihara T, Hoshino T, Gotoh T, Endo M, Sato K, Mizushima T.
Title Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis.
Journal Am J Pathol
Abstract Although recent reports suggest that the endoplasmic 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-1alpha, and Caspase-11 (a positive regulator of interleukin-1beta production) in the intestine was induced with the development of colitis, and this induction was suppressed in CHOP-null mice. ERO-1alpha 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-1alpha, interleukin-1beta production via the induction of Caspase-11, and intestinal mucosal cell apoptosis.
Volume 174(5)
Pages 1786-98
Published 2009-5-1
DOI 10.2353/ajpath.2009.080864
PII S0002-9440(10)61036-X
PMID 19359519
PMC PMC2671267
MeSH Animals Apoptosis / physiology Caspases / genetics Caspases / metabolism Caspases, Initiator Colitis / chemically induced Colitis / etiology* Colitis / pathology* Endoplasmic Reticulum / metabolism* Immunoblotting Interleukin-1beta / genetics Interleukin-1beta / metabolism Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Lipid Peroxidation Macrophage-1 Antigen / genetics Macrophage-1 Antigen / metabolism Macrophages / cytology Macrophages / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Oxidative Stress* Peroxidase / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Reactive Oxygen Species / metabolism* Reverse Transcriptase Polymerase Chain Reaction Thiobarbituric Acid Reactive Substances / metabolism Transcription Factor CHOP / physiology*
IF 3.491
Human and Animal Cells RAW 264(RCB0535)