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

The transient receptor potential vanilloid 1 (TRPV) channel is expressed in human bronchial epithelium (HBE), where it transduces Ca in response to airborne irritants. TRPV 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 expression, localization, and function in the airway epithelium may play a role in bronchiolitis and asthma in childhood. We sought to measure TRPV 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 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 protein expression was higher in HBE from children with versus without asthma and primarily localized to plasma membranes (PMs). During RSV infection, TRPV protein increased more in the PM of asthmatic HBE as compared with nonasthmatic cells. TRPV-mediated increase in intracellular Ca was greater in RSV-infected asthmatic cells, but this increase was attenuated when extracellular Ca was removed. Nerve growth factor (NGF) recapitulated the effect of RSV on TRPV activation in HBE cells. Our data suggest that children with asthma have intrinsically hyperreactive airways due in part to higher TRPV-mediated Ca influx across epithelial membranes, and this abnormality is further exacerbated by NGF overexpression during RSV infection driving additional Ca from intracellular stores.