Modulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections.

Autor:	Mazzone SB; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia., Yang SK; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia., Keller JA; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia., Simanauskaite J; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia., Arikkatt J; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia., Fogarty MJ; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia., Moe AAK; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia., Chen C; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia., Trewella MW; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia., Tian L; Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Ritchie ME; Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Chua BY; The Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia., Phipps S; QIMR Berghofer Medical Research Institute, Herston, QLD, Australia., Short KR; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., McGovern AE; Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2021 Sep 21; Vol. 12, pp. 744812. Date of Electronic Publication: 2021 Sep 21 (Print Publication: 2021).
DOI:	10.3389/fphys.2021.744812
Abstrakt:	Vagal 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Mazzone, Yang, Keller, Simanauskaite, Arikkatt, Fogarty, Moe, Chen, Trewella, Tian, Ritchie, Chua, Phipps, Short and McGovern.)
Databáze:	MEDLINE
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