Helicobacter pylori infection promotes autophagy through Nrf2-mediated heme oxygenase upregulation in human gastric cancer cells.

It has been reported that Helicobacter pylori (H. pylori) infection is one of the primary causes of gastritis and peptic ulcer diseases. More than 50% of the world's population is supposed to be infected by this bacterium. However, 90% of infected patients do not develop gastric cancer, suggesting the existence of host defence mechanisms. Nrf2 is a transcription factor that plays a key role in cellular defence against oxidative stress and inflammation. Autophagy, an autodigestive process that degrades cellular organelles and proteins, plays an important role in maintaining cellular homeostasis. To investigate the molecular mechanisms responsible for cellular adaptive response to H. pylori induced gastric inflammation, human gastric epithelial cells and mice were infected with H. pylori. H. pylori infection induced expression of microtubule-associated light chain3 (LC3), an autophagic marker, through accumulation of reactive oxygen species and subsequently nuclear translocation of the redox-sensitive transcription factor, Nrf2 in human gastric epithelial AGS cells. Furthermore, Nrf2-induced LC3 up-regulation was mediated by heme oxygenase-1 (HO-1) and its by-product, carbon monoxide. Taken together, the Nrf2-HO-1 axis is considered to play a role in cellular adaptive survival response to H. pylori-induced gactric carcinogenesis by inducing autophagy.