Abstract
Thromboxane A2 receptor (TP) mediates bronchial smooth muscle cell (BSMC) contraction, airway hyperresponsiveness,
and airway inflammation in patients with asthma. In the present study, a pathogenic
role of TP activation in airway remodeling was examined using primary cultures of
human BSMC. A TP agonist, I-BOP, concentration-dependently enhanced not only bromodeoxyuridine
(BrdU) uptake but also cell proliferation of BSMC. A TP-selective antagonist, AA-2414,
blocked the effects of I-BOP on both BrdU uptake and cell proliferation. I-BOP-induced
BrdU uptake was significantly blocked by two non-selective tyrosine kinase inhibitors,
genistein and herbimycin A, or a Src family tyrosine kinase inhibitor, PP2, but not
by an inhibitor of epidermal growth factor (EGF) receptor-associated tyrosine kinase,
AG1478. In conclusion, TP receptor activation causes DNA synthesis and cell proliferation
of human BSMC by activating tyrosine kinases including Src, but not by EGF receptor
transactivation.
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Article info
Publication history
Published online: September 06, 2004
Accepted:
July 19,
2004
Received:
April 28,
2004
Footnotes
☆Supported by Grant-in-Aid from Japanese Ministry of Health, Labour and Welfare.
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
