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 a variety of inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00341/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hwai-Jeng Lin |
| collection | DOAJ |
| 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 a variety of 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 to 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. |
| first_indexed | 2024-12-11T16:34:41Z |
| format | Article |
| id | doaj.art-f9e11210966345c0828a6846a833a67e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T16:34:41Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f9e11210966345c0828a6846a833a67e2022-12-22T00:58:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-09-01710.3389/fimmu.2016.00341217133Helicobacter pylori activates HMGB1 expression and recruits RAGE into lipid rafts to promote inflammation in gastric epithelial cellsHwai-Jeng Lin0Fang-Yu Hsu1Wei-Wei Chen2Che-Hsin Lee3Ying-Ju Lin4Yi-Ywan M. Chen5Chih-Jung Chen6Mei-Zi Huang7Min-Chuan Kao8Yu-An Chen9Hsin-Chih Lai10Chih-Ho Lai11Taipei Medical UniversityChina Medical UniversityChina Medical UniversityChina Medical UniversityChina Medical University and HospitalChang Gung UniversityChang Gung Memorial HospitalChang Gung UniversityChang Gung UniversityChina Medical UniversityChang Gung UniversityChang Gung UniversityHelicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates a variety of 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 to 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00341/fullCholesterolHelicobacter pyloriInterleukin-8RageHMGB1 |
| spellingShingle | 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 Helicobacter pylori activates HMGB1 expression and recruits RAGE into lipid rafts to promote inflammation in gastric epithelial cells Frontiers in Immunology Cholesterol Helicobacter pylori Interleukin-8 Rage HMGB1 |
| 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 | Cholesterol Helicobacter pylori Interleukin-8 Rage HMGB1 |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00341/full |
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