Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis

Takushi Namba, Ken Ichiro Tanaka, Yosuke Ito, Tomoaki Ishihara, Tatsuya Hoshino, Tomomi Gotoh, Motoyoshi Endo, Keizo Sato, Tohru Mizushima

Research output: Contribution to journalArticle

71 Citations (Scopus)

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-1α, and Caspase-11 (a positive regulator of interleukin-1β production) in the intestine was induced with the development of colitis, and this induction was suppressed in CHOP-null mice. ERO-1α 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-1α, interleukin-1β production via the induction of Caspase-11, and intestinal mucosal cell apoptosis.

Original languageEnglish
Pages (from-to)1786-1798
Number of pages13
JournalAmerican Journal of Pathology
Volume174
Issue number5
DOIs
Publication statusPublished - 2009 May
Externally publishedYes

Fingerprint

Transcription Factor CHOP
CCAAT-Enhancer-Binding Proteins
Endoplasmic Reticulum Stress
Colitis
Transcription Factors
Proteins
Reactive Oxygen Species
Interleukin-1
Inflammatory Bowel Diseases
Intestines
Macrophages
Apoptosis
Caspase 1
Intestinal Mucosa
Caspases
Up-Regulation
Cell Count
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis. / Namba, Takushi; Tanaka, Ken Ichiro; Ito, Yosuke; Ishihara, Tomoaki; Hoshino, Tatsuya; Gotoh, Tomomi; Endo, Motoyoshi; Sato, Keizo; Mizushima, Tohru.

In: American Journal of Pathology, Vol. 174, No. 5, 05.2009, p. 1786-1798.

Research output: Contribution to journalArticle

Namba, Takushi ; Tanaka, Ken Ichiro ; Ito, Yosuke ; Ishihara, Tomoaki ; Hoshino, Tatsuya ; Gotoh, Tomomi ; Endo, Motoyoshi ; Sato, Keizo ; Mizushima, Tohru. / Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis. In: American Journal of Pathology. 2009 ; Vol. 174, No. 5. pp. 1786-1798.
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