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Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

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-produ...

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Autores principales: Lin, Hwai-Jeng, Hsu, Fang-Yu, Chen, Wei-Wei, Lee, Che-Hsin, Lin, Ying-Ju, Chen, Yi-Ywan M., Chen, Chih-Jung, Huang, Mei-Zi, Kao, Min-Chuan, Chen, Yu-An, Lai, Hsin-Chih, Lai, Chih-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016528/
https://www.ncbi.nlm.nih.gov/pubmed/27667993
http://dx.doi.org/10.3389/fimmu.2016.00341
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author Lin, Hwai-Jeng
Hsu, Fang-Yu
Chen, Wei-Wei
Lee, Che-Hsin
Lin, Ying-Ju
Chen, Yi-Ywan M.
Chen, Chih-Jung
Huang, Mei-Zi
Kao, Min-Chuan
Chen, Yu-An
Lai, Hsin-Chih
Lai, Chih-Ho
author_facet Lin, Hwai-Jeng
Hsu, Fang-Yu
Chen, Wei-Wei
Lee, Che-Hsin
Lin, Ying-Ju
Chen, Yi-Ywan M.
Chen, Chih-Jung
Huang, Mei-Zi
Kao, Min-Chuan
Chen, Yu-An
Lai, Hsin-Chih
Lai, Chih-Ho
author_sort Lin, Hwai-Jeng
collection PubMed
description 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.
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spelling pubmed-50165282016-09-23 Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells Lin, Hwai-Jeng Hsu, Fang-Yu Chen, Wei-Wei Lee, Che-Hsin Lin, Ying-Ju Chen, Yi-Ywan M. Chen, Chih-Jung Huang, Mei-Zi Kao, Min-Chuan Chen, Yu-An Lai, Hsin-Chih Lai, Chih-Ho Front Immunol Immunology 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. Frontiers Media S.A. 2016-09-09 /pmc/articles/PMC5016528/ /pubmed/27667993 http://dx.doi.org/10.3389/fimmu.2016.00341 Text en Copyright © 2016 Lin, Hsu, Chen, Lee, Lin, Chen, Chen, Huang, Kao, Chen, Lai and Lai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lin, Hwai-Jeng
Hsu, Fang-Yu
Chen, Wei-Wei
Lee, Che-Hsin
Lin, Ying-Ju
Chen, Yi-Ywan M.
Chen, Chih-Jung
Huang, Mei-Zi
Kao, Min-Chuan
Chen, Yu-An
Lai, Hsin-Chih
Lai, Chih-Ho
Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title_full Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title_fullStr Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title_full_unstemmed Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title_short Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells
title_sort helicobacter pylori activates hmgb1 expression and recruits rage into lipid rafts to promote inflammation in gastric epithelial cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016528/
https://www.ncbi.nlm.nih.gov/pubmed/27667993
http://dx.doi.org/10.3389/fimmu.2016.00341
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