Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor.
Br J Pharmacol
; 181(13): 1916-1934, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38430056
ABSTRACT
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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 ß2-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
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Estimulação do Nervo Vago
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Receptor Nicotínico de Acetilcolina alfa7
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Camundongos Endogâmicos BALB C
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article