title: Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells.
abstract: Receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (TRPV1), transient receptor potential cation channel, Subfamily A, Member 1 (TRPA1) and acid sensing ion channel receptor 3 (ASIC3). Respiratory viruses, such as respiratory syncytial virus (RSV) and measles virus (MV) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. We used in vitro models of sensory neurones (SHSY5Y or differentiated IMR-32 cells) and human bronchial epithelium (BEAS-2B cells) as well as primary human bronchial epithelial cells (PBEC) to study the effect of MV and RSV infection on receptor expression. Receptor mRNA and protein levels were examined by qPCR and flow cytometry, respectively, following infection or treatment with UV inactivated virus, virus-induced soluble factors or pelleted virus. Concentrations of a range of cytokines in resultant BEAS-2B and PBEC supernatants were determined by ELISA. Up-regulation of TRPV1, TRPA1 and ASICS3 expression occurred by 12 hours post-infection in each cell type. This was independent of replicating virus, within the same cell, as virus-induced soluble factors alone were sufficient to increase channel expression. IL-8 and IL-6 increased in infected cell supernatants. Antibodies against these factors inhibited TRP receptor up-regulation. Capsazepine treatment inhibited virus induced up-regulation of TRPV1 indicating that these receptors are targets for treating virus-induced cough.
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Shadia
authors.initials: S
authors.lastname: Omar
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Haniah
authors.initials: H
authors.lastname: Abdullah
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Brady
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Corry
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Hanagh
authors.initials: H
authors.lastname: Winter
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Olivier
authors.initials: O
authors.lastname: Touzelet
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Ultan F
authors.initials: UF
authors.lastname: Power
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Lundy
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: Lorcan P A
authors.initials: LP
authors.lastname: McGarvey
authors.affiliation: Queen's University Belfast, Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Belfast, United Kingdom.
authors.forename: S Louise
authors.identifier: http://orcid.org/0000-0002-2617-8603
authors.initials: SL
authors.lastname: Cosby
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008457:Measles / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels