乙酰甲胆碱
医学
迷走神经电刺激
支气管肺泡灌洗
免疫学
屋尘螨
炎症
烟碱激动剂
迷走神经
内分泌学
刺激
内科学
受体
肺
过敏
呼吸道疾病
过敏原
作者
Caroline Sévoz‐Couche,Wupeng Liao,Hazel Yu Ci Foo,Isabelle Bonne,Lu Thong Beng,Caris Tan Qi Hui,Wendy Yen Xian Peh,Yen Shih-Cheng,Wai Shui Fred Wong
出处
期刊:Authorea - Authorea
日期:2023-03-08
标识
DOI:10.22541/au.167827293.36362259/v1
摘要
Background and Purpose Asthma is characterized by airway inflammation, mucus hypersecretion and airway hyperresponsiveness (AHR). The activation of cholinergic anti‐inflammatory pathway (CAP) through nicotinic agents has been shown to control 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 (5Hz, 0.5 ms, 0.1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy. AHR in response to methacholine was also measured. Key Results In the HDM mouse asthma model, active but not sham VNS reduced BAL fluid total and differential cell counts, blocked mucus hypersecretion and suppressed choline acetyltransferase (ChAT) expression in bronchial epithelial cells. Besides, active VNS also abated HDM-induced elevation of type 2 cytokines IL-4 and IL-5. Furthermore, goblet cell hyperplasia and collagen deposition were diminished in VNS-treated mice. Mechanistically, VNS was found to block the phosphorylation of transcription factor STAT6 and the level of IRF4 in total lung lysates. Finally, VNS abrogated methacholine-induced AHR in asthma mice. Therapeutic effects of VNS were abolished by prior administration with α-bungarotoxin, a specific inhibitor of α7 nicotinic receptors (α7nAChR). Conclusion 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 through α7nAChR.
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