title: Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma.
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.
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom. Electronic address: l.mcgarvey@qub.ac.uk.
authors.forename: Lorcan P
authors.initials: LP
authors.lastname: McGarvey
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Butler
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Stokesberry
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Liam
authors.initials: L
authors.lastname: Polley
authors.affiliation: Tissue Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Hani'ah
authors.initials: H
authors.lastname: Abdullah
authors.affiliation: Centre for Vision and Vascular Science, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ashraf
authors.affiliation: Centre for Vision and Vascular Science, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Mary K
authors.initials: MK
authors.lastname: McGahon
authors.affiliation: Centre for Vision and Vascular Science, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Curtis
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Joe
authors.initials: J
authors.lastname: Arron
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: David
authors.initials: D
authors.lastname: Choy
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Warke
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Ennis
authors.affiliation: Centre for Vision and Vascular Science, Queens University Belfast, Belfast, United Kingdom; Institute of Biology, Taras Shevchenko Kiev National University, Kiev, Ukraine.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zholos
authors.affiliation: Department of Respiratory, Otolaryngology and Molecular Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
authors.affiliation: Centre for Infection and Immunity, Health Sciences Building, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Liam G
authors.initials: LG
authors.lastname: Heaney
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000737:chemistry*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050916:TRPV Cation Channels / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human
keywords: Ion channel; asthma; chemical; cough; exacerbation; irritant; sensory