Rhinovirus-induced exacerbations of asthma: How is the {beta}2-adrenoceptor implicated?
Rhinovirus (RV) infections are the major cause of asthma exacerbations in children and adults. Under normal circumstances, asthmatic airway obstruction improves spontaneously or characteristically briskly in response to inhaled beta(2)-adrenergic receptor (beta(2)AR) agonists. During virus-associated exacerbations, an impaired response to beta(2)AR agonists is observed; the reason for this is not known. The objective of this study was to determine the effect of RV infection on airway smooth muscle beta(2)AR function. The human cell line Beas-2B and primary human bronchial epithelial cells (HBECs) were infected with RV (multiplicity of infection = 1). After 1 or 5 days for primary and Beas-2B cells, respectively, cell culture supernatants were harvested, UV-irradiated to inactivate RV, and applied to human airway smooth muscle cells for 3 days to assess modifications of beta(2)AR function. RV conditioned medium from Beas-2B and HBECs decreased beta(2)AR agonist-induced cAMP by 50 and 65%, respectively (n = 5; P < 0.05). When cAMP was induced independently of the beta(2)AR using forskolin, no impairment was found. Using flow cytometry, we demonstrated that this decrease was likely the result of beta(2)AR desensitization because membrane but not total cell receptor beta(2)AR was decreased. Pretreatment of HBECs and Beas-2B cells but not human airway smooth muscle cells with the corticosteroids dexamethasone or fluticasone abolished virus-mediated beta(2)AR loss of function. This study shows that epithelial infection with RV induces a decrease of beta(2)AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of beta(2)AR agonist function during RV-induced asthma exacerbations.
The University of Sydney, NSW, Australia. thomastrian@med.usyd.edu.au
Thomas
T
Trian
Lyn M
LM
Moir
Qi
Q
Ge
Janette K
JK
Burgess
Curtis
C
Kuo
Nicholas J C
NJ
King
Helen K
HK
Reddel
Judith L
JL
Black
Brian G
BG
Oliver
Brent E
BE
McParland
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000150:complications* / Q000821:virology*; D001980:Bronchi / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010850:Picornaviridae Infections / Q000150:complications / Q000821:virology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012229:Rhinovirus / Q000378:metabolism*
D017077:Culture Media, Conditioned; D018343:Receptors, Adrenergic, beta-2