title: Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.
abstract: Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Sami
authors.initials: S
authors.lastname: Shariff
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Shelfoon
authors.affiliation: 2 School of Life Sciences, University of Lincoln, Lincoln, United Kingdom; and.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Holden
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Traves
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shahina
authors.initials: S
authors.lastname: Wiehler
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Cora
authors.initials: C
authors.lastname: Kooi
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Proud
authors.affiliation: 1 Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|3 Department of Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
mesh_terms: D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D037342:Pertussis Toxin / Q000633:toxicity; D010850:Picornaviridae Infections / Q000473:pathology / Q000821:virology*; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
chemical_list: D018946:Chemokine CCL5; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D000242:Cyclic AMP; D037342:Pertussis Toxin
keywords: CCL5; airway epithelial cell; airway smooth muscle; chemotaxis; rhinovirus