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Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation
The receptor for advanced glycation end products (RAGE) interacts with various molecules in the cell membrane to induce an inflammatory response. The cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399302/ https://www.ncbi.nlm.nih.gov/pubmed/30863392 http://dx.doi.org/10.3389/fimmu.2019.00109 |
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author | Lin, Hwai-Jeng Jiang, Zhi-Pei Lo, Horng-Ren Feng, Chun-Lung Chen, Chih-Jung Yang, Chia-Yu Huang, Mei-Zi Wu, Hui-Yu Chen, Yu-An Chen, Yu Chiu, Cheng-Hsun Lai, Chih-Ho |
author_facet | Lin, Hwai-Jeng Jiang, Zhi-Pei Lo, Horng-Ren Feng, Chun-Lung Chen, Chih-Jung Yang, Chia-Yu Huang, Mei-Zi Wu, Hui-Yu Chen, Yu-An Chen, Yu Chiu, Cheng-Hsun Lai, Chih-Ho |
author_sort | Lin, Hwai-Jeng |
collection | PubMed |
description | The receptor for advanced glycation end products (RAGE) interacts with various molecules in the cell membrane to induce an inflammatory response. The cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with membrane lipid rafts, by which CdtB enters the nucleus to induce pathogenesis. In this study, we first explored the relationships between RAGE, lipid rafts, and inflammation in gastrointestinal epithelial cells exposed to CDT. Our results showed that CDT activated the expression of RAGE and high mobility group box 1 (HMGB1), followed by the recruitment of RAGE into lipid rafts. In contrast, RAGE antagonist inhibited CDT-induced inflammation via the RAGE-HMGB1 axis. Disruption of lipid rafts decreased CDT-induced downstream signaling, which in turn attenuated the inflammatory response. Furthermore, in vivo studies revealed severe inflammation and upregulation of RAGE and IL-1β in the intestinal tissues of CDT-treated mice. These results demonstrate that mobilization of RAGE to lipid rafts plays a crucial role in CDT-induced inflammation. |
format | Online Article Text |
id | pubmed-6399302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63993022019-03-12 Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation Lin, Hwai-Jeng Jiang, Zhi-Pei Lo, Horng-Ren Feng, Chun-Lung Chen, Chih-Jung Yang, Chia-Yu Huang, Mei-Zi Wu, Hui-Yu Chen, Yu-An Chen, Yu Chiu, Cheng-Hsun Lai, Chih-Ho Front Immunol Immunology The receptor for advanced glycation end products (RAGE) interacts with various molecules in the cell membrane to induce an inflammatory response. The cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with membrane lipid rafts, by which CdtB enters the nucleus to induce pathogenesis. In this study, we first explored the relationships between RAGE, lipid rafts, and inflammation in gastrointestinal epithelial cells exposed to CDT. Our results showed that CDT activated the expression of RAGE and high mobility group box 1 (HMGB1), followed by the recruitment of RAGE into lipid rafts. In contrast, RAGE antagonist inhibited CDT-induced inflammation via the RAGE-HMGB1 axis. Disruption of lipid rafts decreased CDT-induced downstream signaling, which in turn attenuated the inflammatory response. Furthermore, in vivo studies revealed severe inflammation and upregulation of RAGE and IL-1β in the intestinal tissues of CDT-treated mice. These results demonstrate that mobilization of RAGE to lipid rafts plays a crucial role in CDT-induced inflammation. Frontiers Media S.A. 2019-02-26 /pmc/articles/PMC6399302/ /pubmed/30863392 http://dx.doi.org/10.3389/fimmu.2019.00109 Text en Copyright © 2019 Lin, Jiang, Lo, Feng, Chen, Yang, Huang, Wu, Chen, Chen, Chiu 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) and the copyright owner(s) 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 Jiang, Zhi-Pei Lo, Horng-Ren Feng, Chun-Lung Chen, Chih-Jung Yang, Chia-Yu Huang, Mei-Zi Wu, Hui-Yu Chen, Yu-An Chen, Yu Chiu, Cheng-Hsun Lai, Chih-Ho Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title | Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title_full | Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title_fullStr | Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title_full_unstemmed | Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title_short | Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation |
title_sort | coalescence of rage in lipid rafts in response to cytolethal distending toxin-induced inflammation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399302/ https://www.ncbi.nlm.nih.gov/pubmed/30863392 http://dx.doi.org/10.3389/fimmu.2019.00109 |
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