Identification of sodium salicylate as an hsp inducer using a simple screening system for stress response modulators in mammalian cells.

As heat shock proteins (Hsps) are involved in protecting cells and also in the pathophysiology of diseases such as inflammation, cancer and neurodegenerative disorders, modulators of Hsp expression in mammalian cells would seem to be useful for the treatment of various diseases. In this study, we isolated mammalian cell lines for screening of Hsp modulators; mouse C3H10T1/2 cells stably transfected with a plasmid containing the mouse Hsp105 or human Hsp70B promoter upstream of a luciferase or beta-galactosidase reporter gene, respectively. Using these cells, we examined the effect of sodium salicylate (SA), which may induce the transcription of hsp genes, on stress response in mammalian cells. When these cells were treated with SA for 1 h at 37 degrees C, both promoter activities were up-regulated by SA at concentrations of more than 45 mm. The activation of heat shock factor and the subsequent accumulation of Hsp105alpha and Hsp70 were detected in cells treated with SA at concentrations of more than 20 and 45 mm, respectively. Furthermore, SA induced resistance against a subsequent lethal stress. These findings suggested that SA is a potent hsp inducer, and may be used to protect cells against deleterious stressors.