Human rhinovirus infection of epithelial cells modulates airway smooth muscle migration

Shariff, Sami, Shelfoon, Christopher, Holden, Neil S. , Traves, Suzanne L., Wiehler, Shahina, Kooi, Cora, Proud, David and Leigh, Richard (2017) Human rhinovirus infection of epithelial cells modulates airway smooth muscle migration. American Journal of Respiratory Cell and Molecular Biology, 56 (6). pp. 796-803. ISSN 1044-1549

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Rationale: 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 mass with a greater proximity of the airway smooth muscle cells (ASMC) to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMC. Methods: ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer. Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8 and CXCL10 were also examined. Results: Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pre-treatment of ASMC with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were 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. Conclusion: These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis, and thus may contribute to the pathogenesis of airway remodeling in asthmatic patients.

Keywords:Airway epithelial cell, Airway smooth muscle, Chemotaxis, CCL5
Subjects:B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology
Divisions:College of Science > School of Life Sciences
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ID Code:26853
Deposited On:28 Mar 2017 09:17

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