RT Journal Article
SR Electronic
T1 Rhinovirus induces MUC5AC in a human infection model, &amp; <em>in vitro</em> <em>via</em> NF-κB &amp; EGFR pathways
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj00269-2010
DO 10.1183/09031936.00026910
A1 C.A. Hewson
A1 J.J. Haas
A1 N.W. Bartlett
A1 S.D. Message
A1 V. Laza-Stanca
A1 T. Kebadze
A1 G. Caramori
A1 J. Zhu
A1 M.R. Edbrooke
A1 L.A. Stanciu
A1 O.M. Kon
A1 A. Papi
A1 P.K. Jeffery
A1 M.R. Edwards
A1 S.L. Johnston
YR 2010
UL http://erj.ersjournals.com/content/early/2010/06/04/09031936.00026910.abstract
AB Rhinovirus (RV) infections are the major cause of asthma exacerbations - the major cause of morbidity and mortality in asthma. MUC5AC is the major mucin produced by bronchial epithelial cells. Whether RV infection up-regulates MUC5AC in vivo is unknown, and the molecular mechanisms involved incompletely understood.We investigated RV induction of MUC5AC in vivo and in vitro to identify targets for development of new therapies for asthma exacerbations.RV infection increased MUC5AC release in normal and asthmatic volunteers experimentally infected with RV-16; and in asthmatic, but not normal subjects, this was related to virus load. Bronchial epithelial cells were confirmed a source of MUC5AC in vivo. RV induction of MUC5AC in bronchial epithelial cells in vitro occurred via nuclear factor-κB dependent induction of matrix metalloproteinase mediated transforming growth factor-α release, thereby activating an epidermal growth factor receptor-dependent cascade culminating, via mitogen-activated protein kinase activation, in specificity protein-1 trans-activation of the MUC5AC promoter.RV induction of MUC5AC may be an important mechanism in RV-induced asthma exacerbations in vivo. Revealing the complex serial signalling cascade involved identifies targets for development of pharmacologic intervention to treat mucus hyper secretion in RV induced illness.