Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor.

asthma bronchoalveolar inflammation nicotinic receptors vagus nerve stimulation

Journal

British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536

Informations de publication

Date de publication:
02 Mar 2024
Historique:
revised: 24 11 2023
received: 08 03 2023
accepted: 08 01 2024
medline: 2 3 2024
pubmed: 2 3 2024
entrez: 2 3 2024
Statut: aheadofprint

Résumé

Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown. BALB/c mice were sensitized and challenged with house dust mite (HDM) extract and treated with active VNS (5 Hz, 0.5 ms, 0.05-1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy. In the HDM mouse asthma model, VNS at intensities equal to or above 0.1 mA (VNS 0.1) but not sham VNS reduced BAL fluid differential cell counts and alveolar macrophages expressing α7 nicotinic receptors (α7nAChR), goblet cell hyperplasia, and collagen deposition. Besides, VNS 0.1 also abated HDM-induced elevation of type 2 cytokines IL-4 and IL-5 and was found to block the phosphorylation of transcription factor STAT6 and expression level of IRF4 in total lung lysates. Finally, VNS 0.1 abrogated methacholine-induced hyperresponsiveness in asthma mice. Prior administration of α-bungarotoxin, a specific inhibitor of α7nAChR, but not propranolol, a specific inhibitor of β2-adrenoceptors, abolished the therapeutic effects of VNS 0.1. Our data revealed the protective effects of VNS on various clinical features in allergic airway inflammation model. VNS, a clinically approved therapy for depression and epilepsy, appears to be a promising new strategy for controlling allergic asthma.

Sections du résumé

BACKGROUND AND PURPOSE OBJECTIVE
Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown.
EXPERIMENTAL APPROACH METHODS
BALB/c mice were sensitized and challenged with house dust mite (HDM) extract and treated with active VNS (5 Hz, 0.5 ms, 0.05-1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy.
KEY RESULTS RESULTS
In the HDM mouse asthma model, VNS at intensities equal to or above 0.1 mA (VNS 0.1) but not sham VNS reduced BAL fluid differential cell counts and alveolar macrophages expressing α7 nicotinic receptors (α7nAChR), goblet cell hyperplasia, and collagen deposition. Besides, VNS 0.1 also abated HDM-induced elevation of type 2 cytokines IL-4 and IL-5 and was found to block the phosphorylation of transcription factor STAT6 and expression level of IRF4 in total lung lysates. Finally, VNS 0.1 abrogated methacholine-induced hyperresponsiveness in asthma mice. Prior administration of α-bungarotoxin, a specific inhibitor of α7nAChR, but not propranolol, a specific inhibitor of β2-adrenoceptors, abolished the therapeutic effects of VNS 0.1.
CONCLUSION AND IMPLICATIONS CONCLUSIONS
Our data revealed the protective effects of VNS on various clinical features in allergic airway inflammation model. VNS, a clinically approved therapy for depression and epilepsy, appears to be a promising new strategy for controlling allergic asthma.

Identifiants

pubmed: 38430056
doi: 10.1111/bph.16334
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Research Foundation
ID : A-0006243-00-00
Organisme : National University Health System
ID : A-0002851-00-00

Informations de copyright

© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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Auteurs

Caroline Sévoz-Couche (C)

INSERM, UMRS1158 Neurophysiologie Respiratoire et Clinique, Sorbonne Université, Paris, France.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Wupeng Liao (W)

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore.

Hazel Y C Foo (HYC)

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore.

Isabelle Bonne (I)

Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Thong Beng Lu (TB)

Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Caris Tan Qi Hui (C)

Advanced imaging and Histology Core, Immunology Program, Life Science Institute, National University of Singapore, Singapore.

Wendy Yen Xian Peh (WYX)

The N.1 Institute for Health, National University of Singapore, Singapore.
Department of Electrical and Computer Engineering, National University of Singapore, Singapore.

Shi-Cheng Yen (SC)

The N.1 Institute for Health, National University of Singapore, Singapore.
Department of Electrical and Computer Engineering, National University of Singapore, Singapore.

W S Fred Wong (WSF)

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore.
Drug Discovery and Optimization Platform, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Classifications MeSH