The mechanism of heat-shock protein 70 gene expression abolition in gastric epithelium caused by Helicobacter pylori infection

Abstract

Background: The members of the family of heat shock factors coordinate the inducible transcription of heat shock genes in response to diverse stimuli. Any disturbances in signal transduction may lead to the attenuation of heat shock proteins synthesis and to cell death due to apoptosis. It has been shown by others that different nuclear factors, such as nuclear factor interleukin 6 or signal transducer and activator of transcription 3, co-operate with heat shock factors, mostly enhancing their activator effect on heat shock proteins genes expression. Therefore, we sought to determine whether apoptosis induced in the gastric epithelium exposed to live Helicobacter pylori might occur due to the elimination of HSP70 expression and deregulation of the heat shock response of the cell.

Materials and methods: Experiments were performed on KATO III gastric epithelial cells exposed to live cagA, vacA expressing Hp over different periods of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polymerase chain reaction, western-blot, electrophoretic mobility shift assay, decoy and co-immunoprecipitation studies.

Results: We found that in human gastric epithelium exposed to Helicobacter pylori, heat shock factor 1 is bound and restrained in complexes by phosphorylated signal transducer and activator of transcription 3 protein. In consequence, heat shock factor 1 bound up with phosphorylated signal transducer and activator of transcription 3 protein is unable to activate HSP70 protein synthesis in KATO III cells under stress conditions. Helicobacter pylori also causes changes in bax/bcl-2 cellular equilibrium, leading to the induction of apoptosis.

Conclusions: The observed phenomenon might be the mechanism whereby gastric epithelium adapts to the infection of Helicobacter pylori, eliminating cells which are damaged or altered by bacterial cytotoxic products from the tissue.