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 contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with membrane lipid rafts...

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Bibliographic Details
Published in:Frontiers in immunology 2019-02, Vol.10, p.109
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Bacterial Toxins - metabolism
Campylobacter jejuni - metabolism
Cells, Cultured
cytolethal distending toxin
HMGB1
HMGB1 Protein - genetics
HMGB1 Protein - metabolism
Immunology
inflammation
Inflammation - immunology
Interleukin-1beta - metabolism
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
lipid rafts
Male
Membrane Microdomains - genetics
Membrane Microdomains - metabolism
Mice
Mice, Inbred BALB C
RAGE
Receptor for Advanced Glycation End Products - metabolism
Signal Transduction
Up-Regulation
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Summary: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 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, 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00109