Helicobacter pylori activates HMGB1 expression and recruits rage into lipid rafts to promote inflammation in gastric epithelial cells

Hwai Jeng Lin, Fang Yu Hsu, Wei Wei Chen, Che Hsin Lee, Ying Ju Lin, Yi Ywan M Chen, Chih Jung Chen, Mei Zi Huang, Min Chuan Kao, Yu An Chen, Hsin Chih Lai, Chih Ho Lai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases.

Original languageEnglish
Article number341
JournalFrontiers in Immunology
Volume7
Issue numberSEP
DOIs
Publication statusPublished - Sep 9 2016

Keywords

  • Cholesterol
  • Helicobacter pylori
  • HMGB1
  • Interleukin-8
  • RAGE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Lin, H. J., Hsu, F. Y., Chen, W. W., Lee, C. H., Lin, Y. J., Chen, Y. Y. M., Chen, C. J., Huang, M. Z., Kao, M. C., Chen, Y. A., Lai, H. C., & Lai, C. H. (2016). Helicobacter pylori activates HMGB1 expression and recruits rage into lipid rafts to promote inflammation in gastric epithelial cells. Frontiers in Immunology, 7(SEP), [341]. https://doi.org/10.3389/fimmu.2016.00341