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

Autor: 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., 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., 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., 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., 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., Tan Qi Hui C; Advanced imaging and Histology Core, Immunology Program, Life Science Institute, National University of Singapore, Singapore., Azhar SH; Advanced imaging and Histology Core, Immunology Program, Life Science Institute, National University of Singapore, Singapore., Peh WYX; The N.1 Institute for Health, National University of Singapore, Singapore.; Department of Electrical and Computer Engineering, National University of Singapore, Singapore., Yen SC; The N.1 Institute for Health, National University of Singapore, Singapore.; Department of Electrical and Computer Engineering, National University of Singapore, Singapore., 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.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2024 Jul; Vol. 181 (13), pp. 1916-1934. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1111/bph.16334
Abstrakt: Background and Purpose: 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: 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: 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: 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.
(© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
Externí odkaz: