Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways
Abstract Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies;...
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| Format: | Article |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-86069-6 |
| _version_ | 1818722869466628096 |
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| author | Manoj Nair Santosh Jagadeeshan George Katselis Xiaojie Luan Zeinab Momeni Nicolas Henao-Romero Paulos Chumala Julian S. Tam Yasuhiko Yamamoto Juan P. Ianowski Verónica A. Campanucci |
| author_facet | Manoj Nair Santosh Jagadeeshan George Katselis Xiaojie Luan Zeinab Momeni Nicolas Henao-Romero Paulos Chumala Julian S. Tam Yasuhiko Yamamoto Juan P. Ianowski Verónica A. Campanucci |
| author_sort | Manoj Nair |
| collection | DOAJ |
| description | Abstract Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood. We hypothesize that RAGE contributes to electrophysiological and biochemical changes in tDRGs during inflammation. We used tDRGs and tracheas from wild types (WT), RAGE knock-out (RAGE-KO), and with the RAGE antagonist FPS-ZM1, and exposed them to lipopolysaccharides (LPS). We studied: capsaicin (CAP)-evoked currents and action potentials (AP), tracheal submucosal gland secretion, RAGE expression and downstream pathways. In WT neurons, LPS increased CAP-evoked currents and AP generation, and it caused submucosal gland hypersecretion in tracheas from WT mice exposed to LPS. In contrast, LPS had no effect on tDRG excitability or gland secretion in RAGE-KO mice or mice treated with FPS-ZM1. LPS upregulated full-length RAGE (encoded by Tv1-RAGE) and downregulated a soluble (sRAGE) splice variant (encoded by MmusRAGEv4) in tDRG neurons. These data suggest that sensitization of tDRG neurons contributes to hypersecretion in the upper airways during inflammation. And at least two RAGE variants may be involved in these effects of LPS. |
| first_indexed | 2024-12-17T21:01:29Z |
| format | Article |
| id | doaj.art-791185a6714e4c919fa945c245e250ba |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T21:01:29Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-791185a6714e4c919fa945c245e250ba2022-12-21T21:32:43ZengNature PortfolioScientific Reports2045-23222021-04-0111111610.1038/s41598-021-86069-6Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airwaysManoj Nair0Santosh Jagadeeshan1George Katselis2Xiaojie Luan3Zeinab Momeni4Nicolas Henao-Romero5Paulos Chumala6Julian S. Tam7Yasuhiko Yamamoto8Juan P. Ianowski9Verónica A. Campanucci10Department of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanDepartment of Medicine, College of Medicine, University of SaskatchewanDepartment of Medicine, College of Medicine, University of SaskatchewanDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanDepartment of Medicine, College of Medicine, University of SaskatchewanDepartment of Medicine, Division of Respirology, College of Medicine, University of SaskatchewanDepartment of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical ScienceDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of SaskatchewanAbstract Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood. We hypothesize that RAGE contributes to electrophysiological and biochemical changes in tDRGs during inflammation. We used tDRGs and tracheas from wild types (WT), RAGE knock-out (RAGE-KO), and with the RAGE antagonist FPS-ZM1, and exposed them to lipopolysaccharides (LPS). We studied: capsaicin (CAP)-evoked currents and action potentials (AP), tracheal submucosal gland secretion, RAGE expression and downstream pathways. In WT neurons, LPS increased CAP-evoked currents and AP generation, and it caused submucosal gland hypersecretion in tracheas from WT mice exposed to LPS. In contrast, LPS had no effect on tDRG excitability or gland secretion in RAGE-KO mice or mice treated with FPS-ZM1. LPS upregulated full-length RAGE (encoded by Tv1-RAGE) and downregulated a soluble (sRAGE) splice variant (encoded by MmusRAGEv4) in tDRG neurons. These data suggest that sensitization of tDRG neurons contributes to hypersecretion in the upper airways during inflammation. And at least two RAGE variants may be involved in these effects of LPS.https://doi.org/10.1038/s41598-021-86069-6 |
| spellingShingle | Manoj Nair Santosh Jagadeeshan George Katselis Xiaojie Luan Zeinab Momeni Nicolas Henao-Romero Paulos Chumala Julian S. Tam Yasuhiko Yamamoto Juan P. Ianowski Verónica A. Campanucci Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways Scientific Reports |
| title | Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| title_full | Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| title_fullStr | Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| title_full_unstemmed | Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| title_short | Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| title_sort | lipopolysaccharides induce a rage mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways |
| url | https://doi.org/10.1038/s41598-021-86069-6 |
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