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dc.contributor.authorMazzone, Stuart B
dc.contributor.authorYang, Seung-Kwon
dc.contributor.authorKeller, Jennifer A
dc.contributor.authorSimanauskaite, Juste
dc.contributor.authorArikkatt, Jaisy
dc.contributor.authorFogarty, Matthew J
dc.contributor.authorMoe, Aung Aung Kywe
dc.contributor.authorChen, Chen
dc.contributor.authorTrewella, Matthew W
dc.contributor.authorTian, Luyi
dc.contributor.authorRitchie, Matthew E
dc.contributor.authorChua, Brendan Y
dc.contributor.authorPhipps, Simon
dc.contributor.authorShort, Kirsty R
dc.contributor.authorMcGovern, Alice E
dc.date.accessioned2022-06-24T01:36:34Z
dc.date.available2022-06-24T01:36:34Z
dc.date.issued2021
dc.identifier.issn1664-042X
dc.identifier.doi10.3389/fphys.2021.744812
dc.identifier.urihttp://hdl.handle.net/10072/415570
dc.description.abstractVagal sensory neurons contribute to the symptoms and pathogenesis of inflammatory pulmonary diseases through processes that involve changes to their morphological and functional characteristics. The alarmin high mobility group box-1 (HMGB1) is an early mediator of pulmonary inflammation and can have actions on neurons in a range of inflammatory settings. We hypothesized that HMGB1 can regulate the growth and function of vagal sensory neurons and we set out to investigate this and the mechanisms involved. Culturing primary vagal sensory neurons from wildtype mice in the presence of HMGB1 significantly increased neurite outgrowth, while acute application of HMGB1 to isolated neurons under patch clamp electrophysiological investigation produced inward currents and enhanced action potential firing. Transcriptional analyses revealed the expression of the cognate HMGB1 receptors, Receptor for Advanced Glycation End products (RAGE) and Toll-like Receptor 4 (TLR4), in subsets of vagal sensory neurons. HMGB1-evoked growth and electrophysiological responses were significantly reduced in primary vagal sensory neurons harvested from RAGE deficient mice and completely absent in neurons from RAGE/TLR4 double deficient mice. Immunohistochemical analysis of vagal sensory neurons collected from mice after intranasal infection with murine pneumovirus or influenza A virus (IAV), or after intratracheal administration with the viral mimetic PolyI:C, revealed a significant increase in nuclear-to-cytoplasm translocation of HMGB1 compared to mock-inoculated mice. Neurons cultured from virus infected wildtype mice displayed a significant increase in neurite outgrowth, which was not observed for neurons from virus infected RAGE or RAGE/TLR4 deficient mice. These data suggest that HMGB1 can enhance vagal sensory neuron growth and excitability, acting primarily via sensory neuron RAGE. Activation of the HMGB1-RAGE axis in vagal sensory neurons could be an important mechanism leading to vagal hyperinnervation and hypersensitivity in chronic pulmonary disease.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherFrontiers Media SA
dc.relation.ispartofpagefrom744812
dc.relation.ispartofjournalFrontiers in Physiology
dc.relation.ispartofvolume12
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchPsychology
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode52
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsPhysiology
dc.subject.keywordsvagal ganglia
dc.subject.keywordsvisceral sensory
dc.titleModulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationMazzone, SB; Yang, S-K; Keller, JA; Simanauskaite, J; Arikkatt, J; Fogarty, MJ; Moe, AAK; Chen, C; Trewella, MW; Tian, L; Ritchie, ME; Chua, BY; Phipps, S; Short, KR; McGovern, AE, Modulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections, Frontiers in Physiology, 2021, 12, pp. 744812
dcterms.dateAccepted2021-08-19
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2022-06-24T01:27:18Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 Mazzone, Yang, Keller, Simanauskaite, Arikkatt, Fogarty, Moe, Chen, Trewella, Tian, Ritchie, Chua, Phipps, Short and McGovern. 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.
gro.hasfulltextFull Text
gro.griffith.authorChen, Chen


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