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. 2014 Mar;133(3):704-12.e4.
doi: 10.1016/j.jaci.2013.09.016. Epub 2013 Nov 8.

Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma

Lorcan P McGarvey  1 , Claire A Butler  2 , Susan Stokesberry  2 , Liam Polley  2 , Stephen McQuaid  3 , Hani'ah Abdullah  2 , Sadaf Ashraf  4 , Mary K McGahon  4 , Tim M Curtis  4 , Joe Arron  5 , David Choy  5 , Tim J Warke  2 , Peter Bradding  6 , Madeleine Ennis  2 , Alexander Zholos  7 , Richard W Costello  8 , Liam G Heaney  2
Affiliations

Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma

Lorcan P McGarvey et al. J Allergy Clin Immunol. 2014 Mar.

Abstract

Background: The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma. The functional expression of TRPV1 on airway epithelium has yet to be elucidated.

Objective: In this study we examined the molecular, functional, and immunohistochemical expression of TRPV1 in asthmatic and healthy airways.

Methods: Bronchial biopsy specimens and bronchial brushings were obtained from healthy volunteers (n = 18), patients with mild-to-moderate asthma (n = 24), and patients with refractory asthma (n = 22). Cultured primary bronchial epithelial cells from patients with mild asthma (n = 4), nonasthmatic coughers (n = 4), and healthy subjects (n = 4) were studied to investigate the functional role of TRPV1.

Results: Quantitative immunohistochemistry revealed significantly more TRPV1 expression in asthmatic patients compared with healthy subjects, with the greatest expression in patients with refractory asthma (P = .001). PCR and Western blotting analysis confirmed gene and protein expression of TRPV1 in cultured primary bronchial epithelial cells. Patch-clamp electrophysiology directly confirmed functional TRPV1 expression in all 3 groups. In functional assays the TRPV1 agonist capsaicin induced dose-dependent IL-8 release, which could be blocked by the antagonist capsazepine. Reduction of external pH from 7.4 to 6.4 activated a capsazepine-sensitive outwardly rectifying membrane current.

Conclusions: Functional TRPV1 channels are present in the human airway epithelium and overexpressed in the airways of patients with refractory asthma. These channels might represent a novel therapeutic target for the treatment of uncontrolled asthma.

Keywords: Ion channel; asthma; chemical; cough; exacerbation; irritant; sensory.

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