Modulation Of Fibroblast Function By Human Rhinovirus Infected Airway Epithelium
Abstract
Thickening of the lamina reticularis – a feature of airway remodeling in asthma – can be found in the airways of young children with wheeze. In association, wheezing illness due to human rhinovirus infection is an important risk factor for asthma development. We hypothesize that rhinovirus infection may be involved in the pathogenesis of lamina reticularis thickening and, by extension, airway remodeling. We show that upon infection with human rhinovirus the airway epithelium releases chemoattractants that are able to recruit human bronchial fibroblasts – the cell associated with lamina reticularis thickening. CXCL10 and CXCL8 were revealed as key players in this response, broadening their role in asthma pathogenesis. Additionally, fibroblast migration was experimentally abrogated using formoterol and other cAMP elevating agents. Taken together, the work in this thesis supports the hypothesis that rhinovirus infection is involved in the pathogenesis of airway remodeling.