Open AccessRSV infection potentiates TRPV1-mediated calcium transport in bronchial epithelium of asthmatic children
Author(s) -
Terri J. Harford,
L. Grove,
Fariba Rezaee,
Rachel G. Scheraga,
Mitchell A. Olman,
Giovanni Piedimonte
Publication year - 2021
Publication title -
american journal of physiology. lung cellular and molecular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.892
H-Index - 163
eISSN - 1522-1504
pISSN - 1040-0605
DOI - 10.1152/ajplung.00531.2020
Subject(s) - trpv , trpv1 , respiratory epithelium , immunology , asthma , extracellular , ovalbumin , medicine , intracellular , mucus , respiratory system , biology , transient receptor potential channel , microbiology and biotechnology , immune system , receptor , ecology
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.