The Helicobacter Pylori Protein HspB Interferes With Nrf2/Keap1 Pathway Altering The Antioxidant Response of Ags Cells
Buommino E et al. – The results here reported suggest that inhibited nuclear translocation of Nrf2, associated with induced inflammation and increased production of MMPs, might represent a condition enhancing the risk of gastric adenocarcinoma.Methods
- Gene expression in AGS cells transiently and stably transfected was analyzed by real-time PCR.
- Immunoprecipitation and immunofluorescence assays were performed to investigate the ability of H. pylori proteins to interfere with the Nrf2 pathway.
- The authors demonstrated that the H. pylori HspB protein interferes with Nrf2/Keap1 pathway.
- When HspB was transiently transfected in AGS cells, a significant increase in Keap1 gene expression was induced.
- The same result was observed when AGS cells were HspB stably transfected.
- In this case, the increase in Keap1 was associated with reduced gene expression of Nrf2, and of the antioxidant enzymes superoxide dismutase, hemeoxygenase-1, and phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase-1.
- Immunoprecipitation and immunofluorescence assays confirmed the ability of HspB protein to interfere with the Nrf2 pathway.
- Lastly, in HspB-transfected AGS cells, sustained activation of IL-8, COX2, MMP3, and MMP7 was demonstrated.