TY - JOUR
TI - Reducing agents inhibit rhinovirus-induced up-regulation of the
rhinovirus receptor intercellular adhesion molecule-1 (ICAM-1) in
respiratory epithelial cells
AU - Papi, A
AU - Papadopoulos, NG
AU - Stanciu, LA
AU - Bellettato, CM and
AU - Pinamonti, S
AU - Degitz, K
AU - Holgate, ST
AU - Johnston, SL
JO - The FASEB Journal
PY - 2002
VL - 16
TODO - 12
SP - 1934+
PB - Wiley
SN - 0892-6638, 1530-6860
TODO - 10.1096/fj.02-0118fje
TODO - asthma; rhinitis; oxidants; nuclear factor kappa B
TODO - Rhinoviruses are the major cause of common colds and of asthma
exacerbations. Intercellular adhesion molecule-1 (ICAM-1) has a central
role in airway inflammation and is the receptor for 90% of
rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1.
Because redox state is directly implicated in inflammatory responses via
molecular signaling mechanisms, here we studied the effects of reducing
agents on rhinovirus-induced ICAM-1 expression, mRNA upregulation,
promoter activation, and nuclear factor activation. To investigate the
effects of rhinovirus infection on the intracellular redox balance, we
also studied whether rhinovirus infection triggers the production of
reactive oxygen species. We found that reduced (GSH) but not oxidized
(GSSG) glutathione (1-100 muM) inhibited in a dose-dependent manner
rhinovirus-induced ICAM-1 up-regulation and mRNA induction in primary
bronchial and A549 respiratory epithelial cells. GSH but not GSSG also
inhibited rhinovirus-induced ICAM-1 promoter activation and
rhinovirus-induced NF-kappaB activation. In parallel, we found that
rhinovirus infection induced a rapid increase of intracellular
superoxide anion that was maximal at the time of NF-kappaB activation.
This oxidant generation was completely inhibited by GSH. We conclude
that redox-mediated intracellular pathways represent an important target
for the therapeutic control of rhinovirus-induced diseases.
ER -