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Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor
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  • Caroline Sévoz-Couche,
  • Wupeng Liao,
  • Hazel Yu Ci Foo,
  • Isabelle Bonne,
  • Lu Thong Beng,
  • Caris Tan Qi Hui,
  • Wendy Yen Xian Peh,
  • Shih-Cheng Yen,
  • Wai Shui Fred Wong
Caroline Sévoz-Couche
UMR1158

Corresponding Author:[email protected]

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Wupeng Liao
National University of Singapore Yong Loo Lin School of Medicine
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Hazel Yu Ci Foo
National University of Singapore Yong Loo Lin School of Medicine
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Isabelle Bonne
National University of Singapore Yong Loo Lin School of Medicine
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Lu Thong Beng
National University of Singapore Yong Loo Lin School of Medicine
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Caris Tan Qi Hui
National University of Singapore - Kent Ridge Campus
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Wendy Yen Xian Peh
National University of Singapore
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Shih-Cheng Yen
National University of Singapore
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Wai Shui Fred Wong
National University of Singapore Yong Loo Lin School of Medicine
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Abstract

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.
08 Mar 2023Submitted to British Journal of Pharmacology
08 Mar 2023Submission Checks Completed
08 Mar 2023Assigned to Editor
08 Mar 2023Review(s) Completed, Editorial Evaluation Pending
12 Mar 2023Reviewer(s) Assigned
03 May 2023Editorial Decision: Revise Minor
22 Sep 20231st Revision Received