Asthma and lower airway diseaseIncreased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma
Section snippets
Methods
Full methodological details are provided in the Methods section in this article's Online Repository at www.jacionline.org.
Confirmation of TRPV1 expression in cultured human bronchial epithelial cells
Gene expression for multiple members of the TRPV family, including TRPV1 (but not TRPV5), was identified in PBECs from healthy control subjects (n = 3; Fig 1, A). TRPV1 protein was detected at its expected molecular mass of 95 kDa by using Western blotting in the same samples (Fig 1, B).
Microarray
Using gene expression microarray analysis of bronchial brush samples from the Leicester cohort, we found significantly greater TRPV1 expression in patients with severe asthma (median, 0.673; interquartile range
Discussion
In this study, for the first time, we have shown that TRPV1, which is primarily recognized as the major neuronal hot receptor,23, 24 is expressed and functional in human bronchial epithelium. In PBEC cultures we have shown that pharmacologic activation of the TRPV1 channel with capsaicin induces IL-8 release, which can be attenuated by pretreatment with the selective TRPV1 antagonist capsazepine.
Interestingly, TRPV1 expression in the airway was increased in asthmatic patients compared with that
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S.S. was supported by a grant from the Northern Ireland Chest Heart & Stroke Association, and L.P. was supported by a grant from the Higher Education Authority (North South Research Programme). Work in Leicester and Belfast was supported in part by grants from Genentech, South San Francisco, California.
Disclosure of potential conflict of interest: L. P. McGarvey has been supported by one or more grants from the Northern Ireland Chest Heart & Stroke Association and from the Health Education Authority (North South Funding); is a member of advisory boards for Almirall, the NAPP, GlaxoSmithKline (GSK), and Boehringer Ingelheim; has consultancy arrangements with the Endpoint Adjudication Committee (served as Chairman and Committee Member), Boehringer Ingelheim, and GSK; has received one or more grants from or has one or more grants pending with Chiesi, the Laboratory Animal Science Association/NC3Rs, the British Heart Foundation, the Northern Ireland Chest Heart & Stroke Association, Royal Belfast Hospital (Sick Children Clinical Fellowship), Asthma UK, and the Research Forum for the Child International PhD studentships; and has received one or more payments for travel/accommodations/meeting expenses from Chiesi, Boehringer Ingelheim, and GSK. C. A. Butler has received one or more payments for travel/accommodations/meeting expenses from GSK. S. Stokesberry has been supported by one or more grants from the Northern Ireland Chest Heart & Stroke Association. L. Polley has been supported by an educational grant from the Higher Education Authority (North South Research Programme) and has received money from GSK (General Practice Education–Asthma Update [SIGN Guidelines]). J. Arron is employed by and has one or more patents (planned, pending, or issued) with Genentech and owns stock/stock options in Roche Holdings. D. Choy is employed by and owns stock/stock options in Genentech. P. Bradding has been supported by one or more grants from Genentech. M. Ennis has been supported by one or more grants from the Northern Ireland Chest Heart and Stroke Association and from the Higher Education Authority (North South Research Programme). L. G. Heaney has received one or more grants from or has one or more grants pending with GSK, MedImmune, Novartis UK, AstraZeneca, Genenetch, the Medical Research Council UK, the Northern Ireland Chest Heart & Stroke Association, Hoffmann la Roche UK, and Asthma UK/the Northern Ireland Chest Heart & Stroke Association; has received one or more payments for lecturing from or is on the speakers' bureau for GSK, Merck Sharpe & Dohme, Nycomed, Novartis, Genentech Inc and AstraZeneca; and has received one or more payments for travel/accommodations/meeting expenses from AstraZeneca, Chiesi, Novartis, and GSK. The rest of the authors declare that they have no relevant conflicts of interest.