title: Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma.
abstract: Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals.
  
  
  
  Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation.
  
  
  
  CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes.
  
  
  
  Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Baker
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.|Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. HernâniMonteiro, 4200-319, Porto, Portugal.|Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450, Porto, Portugal.
authors.forename: Kristof
authors.initials: K
authors.lastname: Raemdonck
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
authors.forename: Bilel
authors.initials: B
authors.lastname: Dekkak
authors.affiliation: Leukocyte Biology, Imperial College, London, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Snelgrove
authors.affiliation: ArioPharma Limited, Iconix Park, London Road, Pampisford, CB22 3EG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Ford
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
authors.forename: Fisnik
authors.initials: F
authors.lastname: Shala
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.|Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.affiliation: Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK. m.birrell@imperial.ac.uk.|Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK. m.birrell@imperial.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birrell
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D007073:Immunoglobulin E / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D010641:Phenotype; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D039981:Pyroglyphidae / Q000276:immunology; D011914:Rats, Inbred BN; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D015704:CD4 Antigens; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Asthma; Inflammation; Ion channel; Lung