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Inhibition of TRPA1 reduces airway inflammation and hyperresponsiveness in mice with allergic rhinitis
Author(s) -
Fang Zhangfu,
Yi Fang,
Peng Yang,
Zhang Junfeng Jim,
Zhang Liting,
Deng Zheng,
Chen Fagui,
Li Chenhui,
He Yaowei,
Huang Chuqin,
Zhang Qingling,
Lai Kefang,
Xie Jiaxing
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902627r
Subject(s) - airway hyperresponsiveness , medicine , bronchial hyperresponsiveness , inflammation , immunology , airway , allergic inflammation , anesthesia , lung , respiratory disease
This study was conducted to investigate whether a transient receptor potential ankyrin 1 (TRPA1) antagonist (HC‐030031) can reduce airway inflammation and hyperresponsiveness in a murine allergic rhinitis (AR) model. BALB/c mice were sensitized and challenged by ovalbumin (OVA) to induce AR. HC‐030031 or vehicle was administrated to mice via intraperitoneal injection prior to OVA challenges. Nose‐scratching events, histopathologic alterations of the airways, and bronchial hyperresponsiveness (BHR) were assessed. Differential cells and proinflammatory cytokines in the nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluid were measured. Expressions of TRPA1 in nasal mucosa were examined by immunohistochemistry. TRPA1‐expressing vagal neurons were labeled by immunofluorescent staining. HC‐030031‐treated AR mice had markedly reduced type‐2 inflammation in nasal mucosa and ameliorated‐nose‐scratching events than AR mice received vehicle. HC‐030031 treatment also dramatically reduced leucocyte numbers and IL‐8 level in the BAL fluid, inhibited lower airway remodeling and fibrosis, and nearly abolished BHR. HC‐0300031 treatment significantly inhibited the upregulated number of TRPA1 expressing nasal epithelial cells and TRPA1 expressing sensory neurons, leading to downregulation of SP in both upper and lower airways. Targeting TRPA1 may represent a promising strategy for treating AR and AR‐related asthma.