Abstract
Reactive oxygen species (ROS) can regulate the occurrence of autophagy, and effective control of the balance between ROS and autophagy may be an important strategy for Helicobacter pylori induced gastric-related diseases. In this study, infection with H. pylori led to a lower level of ILK phosphorylation and increased ROS generation. Knockdown of ILK enhanced total ROS generation, and upregulated NADPH oxidase (NOX) subunit p22-phox levels. Inhibition of NOXs affected total ROS generation. The inhibition of NOX and ROS generation reduced Nrf2 and HO-1 levels, and knockdown of ILK significantly enhanced Nrf2 levels in H. pylori-infected GES-1 cells. Activation of Nrf2 by DMF decreased ROS levels. Therefore, NOX-dependent ROS production regulated by ILK was essential for activation of Nrf2/HO-1 signaling pathways in H. pylori-infected GES-1 cells. Beclin1, ATG5 and LC3B-II levels were higher both in H. pylori-infected and ILK-knockdown GES-1 cells. In NAC-pretreated GES-1 cells infected with H. pylori, the LC3B-II level was decreased compared to that in cells after H. pylori infection alone. Stable low expression of ILK with further knockdown of Beclin1 or ATG5 significantly reduced LC3B-II levels in GES-1 cells, while with the addition of the autophagy inhibitor chloroquine (CQ), LC3B-II and p62 protein levels were both remarkably upregulated. H. pylori accelerated the accumulation of ROS and further led to the induction of ROS-mediated autophagy by inhibiting ILK levels. Together, these results indicate that H. pylori infection manipulates the NOX-ROS-Nrf2/HO-1-ROS loop to control intracellular oxygen stress and further induced ROS-mediated autophagy by inhibiting ILK levels.
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We thank International Science Editing ( http://www.internationalscienceediting.com ) for editing this manuscript.
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This work was supported by the National Natural Science Foundation of China under Grant [Grant Nos. 82172560 and 81771709], Department of Education of Shandong Province under Grant [Grant No. 2019KJK012] and the Taishan Scholars Program of Shandong Province, China [Grant No. tsqn202211229].
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BL, XL and ZX performed the experiment and drafted the article. JH collected data and analysis. SL and XZ were for data analysis and interpretation. JL and XT were for methodology and software. YZ were for project administration and review and editing the manuscript. All authors have read and agree to be a published version of the final version of the manuscript.
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Li, B., Lv, X., Xu, Z. et al. Helicobacter pylori infection induces autophagy via ILK regulation of NOXs-ROS-Nrf2/HO-1-ROS loop. World J Microbiol Biotechnol 39, 284 (2023). https://doi.org/10.1007/s11274-023-03710-4
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DOI: https://doi.org/10.1007/s11274-023-03710-4