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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Autores principales:	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
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/791185a6714e4c919fa945c245e250ba
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spelling	oai:doaj.org-article:791185a6714e4c919fa945c245e250ba2021-12-02T18:02:48ZLipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways10.1038/s41598-021-86069-62045-2322https://doaj.org/article/791185a6714e4c919fa945c245e250ba2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86069-6https://doaj.org/toc/2045-2322Abstract 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.Manoj NairSantosh JagadeeshanGeorge KatselisXiaojie LuanZeinab MomeniNicolas Henao-RomeroPaulos ChumalaJulian S. TamYasuhiko YamamotoJuan P. IanowskiVerónica A. CampanucciNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	lipopolysaccharides induce a rage-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/791185a6714e4c919fa945c245e250ba
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Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways

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