Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis

Ken Ichiro Tanaka, Takushi Namba, Yasuhiro Arai, Mitsuaki Fujimoto, Hiroaki Adachi, Gen Sobue, Koji Takeuchi, Akira Nakai, Tohru Mizushima

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) involves infiltration of leukocytes into intestinal tissue, resulting in intestinal damage induced by reactive oxygen species (ROS). Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play important roles in this infiltration of leukocytes. The roles of heat shock factor 1 (HSF1) and heat shock proteins (HSPs) in the development of IBD are unclear. In this study, we examined the roles of HSF1 and HSPs in an animal model of IBD, dextran sulfate sodium (DSS)-induced colitis. The colitis worsened or was ameliorated in HSF1-null mice or transgenic mice expressing HSP70 (or HSF1), respectively. Administration of DSS up-regulated the expression of HSP70 in colonic tissues in an HSF1-dependent manner. Expression of pro-inflammatory cytokines and CAMs and the level of cell death observed in colonic tissues were increased or decreased in DSS-treated HSF1-null mice or transgenic mice expressing HSP70, respectively, relative to control wild-type mice. Relative to macrophages from control wildtype mice, macrophages prepared from HSF1-null mice or transgenic mice expressing HSP70 displayed enhanced or reduced activity, respectively, for the generation of pro-inflammatory cytokines in response to lipopolysaccharide stimulation. Suppression of HSF1 or HSP70 expression in vitro stimulated lipopolysaccharide-induced up-regulation of CAMs or ROS-induced cell death, respectively. This study provides the first genetic evidence that HSF1 and HSP70 play a role in protecting against DSS-induced colitis. Furthermore, this protective role seems to involve various mechanisms, such as suppression of expression of pro-inflammatory cytokines and CAMs and ROS-induced cell death.

Original languageEnglish
Pages (from-to)23240-23252
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number32
DOIs
Publication statusPublished - 2007 Aug 10

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis'. Together they form a unique fingerprint.

  • Cite this

    Tanaka, K. I., Namba, T., Arai, Y., Fujimoto, M., Adachi, H., Sobue, G., Takeuchi, K., Nakai, A., & Mizushima, T. (2007). Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis. Journal of Biological Chemistry, 282(32), 23240-23252. https://doi.org/10.1074/jbc.M704081200