title: Loss of classical transient receptor potential 6 channel reduces allergic airway response.
abstract: BACKGROUND
  Non-selective cation influx through canonical transient receptor potential channels (TRPCs) is thought to be an important event leading to airway inflammation. TRPC6 is highly expressed in the lung, but its role in allergic processes is still poorly understood.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the role of TRPC6 in airway hyperresponsiveness (AHR) and allergic inflammation of the lung.
  
  
  METHODS
  Methacholine-induced AHR was assessed by head-out body plethysmography of wild type (WT) and TRPC6(-/-) mice. Experimental airway inflammation was induced by intraperitoneal ovalbumin (OVA) sensitization, followed by OVA aerosol challenges. Allergic inflammation and mucus production were analysed 24 h after the last allergen challenge.
  
  
  RESULTS
  Methacholine-induced AHR and agonist-induced contractility of tracheal rings were increased in TRPC6(-/-) mice compared with WT mice, most probably due to compensatory up-regulation of TRPC3 in airway smooth muscle cells. Most interestingly, when compared with WT mice, TRPC6(-/-) mice exhibited reduced allergic responses after allergen challenge as evidenced by a decrease in airway eosinophilia and blood IgE levels, as well as decreased levels of T-helper type 2 (Th2) cytokines (IL-5, IL-13) in the bronchoalveolar lavage. However, lung mucus production after allergen challenge was not altered by TRPC6 deficiency.
  
  
  CONCLUSIONS
  TRPC6 deficiency inhibits specific allergic immune responses, pointing to an important immunological function of this cation channel in Th2 cells, eosinophils, mast cells and B cells.
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Sel
authors.forename: B R
authors.initials: BR
authors.lastname: Rost
authors.forename: A O
authors.initials: AO
authors.lastname: Yildirim
authors.forename: B
authors.initials: B
authors.lastname: Sel
authors.forename: H
authors.initials: H
authors.lastname: Kalwa
authors.forename: H
authors.initials: H
authors.lastname: Fehrenbach
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: T
authors.initials: T
authors.lastname: Gudermann
authors.forename: A
authors.initials: A
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology; D050052:TRPC Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel; D014132:Trachea / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin