Protective role of HSF1 and HSP70 against gastrointestinal diseases

Abstract

Purpose: It is well known that heat shock proteins (HSPs) are induced by various stressors in order to confer protection against such stressors. Since stressor-induced tissue damage is involved in various diseases, especially gastrointestinal diseases, it has been thought that HSP-inducers are therapeutically beneficial for these diseases. Indirect lines of evidence suggest that HSPs provide a major protective mechanism against irritant-induced gastric lesions. However, no direct evidence exists to support this notion. On the other hand, inflammatory bowel disease (IBD) involves infiltration of leukocytes into intestinal tissue, resulting in intestinal damage. Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play important roles in this infiltration of leukocytes. The roles of heat shock factor 1 (HSF1, a transcription factor for hsp genes) and heat shock proteins (HSPs) in development of IBD are unclear. In this paper, we reviewed our recent work on the role of HSPs in pathogenesis of gastric lesions and IBD by use of HSF1-null mice and transgenic mice expressing Hsp70.

Conclusion: This study provides the first genetic evidence that HSF1 and Hsp70 play a role in protecting against both irritant-induced gastric lesions and IBD-related colitis. The aggravation of irritant-induced gastric lesions in HSF1-null mice is due to their inability to up-regulate Hsp70, leading to apoptosis. On the other hand, this protective role of Hsp70 against colitis seems to involve various mechanisms, such as suppression of expression of pro-inflammatory cytokines and CAMs, and cell death.