RSV infection potentiates TRPV1-mediated calcium transport in bronchial epithelium of asthmatic children

The transient receptor potential vanilloid 1 (TRPV 1 ) channel is expressed in human bronchial epithelium (HBE), where it transduces Ca 2+ in response to airborne irritants. TRPV 1 activation results in bronchoconstriction, cough, and mucus production, and may therefore contribute to the pathophysiology of obstructive airway disease. Since children with asthma face the greatest risk of developing virus-induced airway obstruction, we hypothesized that changes in TRPV 1 expression, localization, and function in the airway epithelium may play a role in bronchiolitis and asthma in childhood. We sought to measure TRPV 1 protein expression, localization, and function in HBE cells from children with versus without asthma, both at baseline and after RSV infection. We determined changes in TRPV 1 protein expression, subcellular localization, and function both at baseline and after RSV infection in primary HBE cells from normal children and children with asthma. Basal TRPV 1 protein expression was higher in HBE from children with versus without asthma and primarily localized to plasma membranes (PMs). During RSV infection, TRPV 1 protein increased more in the PM of asthmatic HBE as compared with nonasthmatic cells. TRPV 1 -mediated increase in intracellular Ca 2+ was greater in RSV-infected asthmatic cells, but this increase was attenuated when extracellular Ca 2+ was removed. Nerve growth factor (NGF) recapitulated the effect of RSV on TRPV 1 activation in HBE cells. Our data suggest that children with asthma have intrinsically hyperreactive airways due in part to higher TRPV 1 -mediated Ca 2+ influx across epithelial membranes, and this abnormality is further exacerbated by NGF overexpression during RSV infection driving additional Ca 2+ from intracellular stores.