Activation of epidermal growth factor receptors is responsible for mucin synthesis
induced by cigarette smoke.
Takeyama, Kiyoshi, Birgit Jung, Jae Jeong Shim, Pierre-Regis Burgel, Trang Dao-Pick,
Iris F. Ueki, Ursula Protin, Peer Kroschel, and Jay A. Nadel.
1Cardiovascular Research Institute and Departments of Medicine and Physiology,
University of California San Francisco, San Francisco, California 94143«hyphen»0130
and 2Department of Pulmonary Research, Boehringer Ingelheim, 55216 Ingelheim,
Germany
APStracts 7:0240L, 2000.
Mucus hypersecretion from hyperplastic airway goblet cells is a hallmark of chronic
obstructive pulmonary disease (COPD). Although cigarette smoking is thought to be
involved in mucus hypersecretion in COPD, the mechanism by which cigarette smoke
induces mucus overproduction is unknown. Here we show that activation of epidermal
growth factor receptors (EGFR) is responsible for mucin production after inhalation of
cigarette smoke in airways in vitro and in vivo. In the airway epithelial cell line NCI-
H292 exposure to cigarette smoke upregulated the EGFR mRNA expression and induced
activation of EGFR-specific tyrosine phosphorylation, resulting in upregulation of
MUC5AC mRNA and protein production, effects that were inhibited completely by
selective EGFR tyrosine kinase inhibitors (BIBX1522, AG-1478) and that were
decreased by antioxidants. In vivo, cigarette smoke inhalation increased MUC5AC
mRNA and goblet cell production in rat airways, effects that were prevented by
pretreatment with BIBX1522. These effects may explain the goblet cell hyperplasia that
occurs in COPD and may provide a novel strategy for therapy in airway hypersecretory
diseases.
Received 1 May 2000; accepted in final form 7 August 2000
APS Manuscript Number L156-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000