Cigarette smoke produces airway wall remodeling in rat tracheal explants.
Small airway remodeling ("small airways disease") is a common finding in cigarette smokers and is an important cause of airflow obstruction. Airway remodeling is usually attributed to the effects of cigarette smoke-induced inflammation in the airway wall, but little is actually known about its pathogenesis. We exposed rat tracheal explants to cigarette smoke and then maintained them in air organ culture. At 24 hours after smoke exposure, there was a dose-dependent increase in gene expression of procollagen and a significant increase in tissue hydroxyproline, a measure of collagen content. Greater increases in procollagen gene expression were found with repeated smoke exposures. Increased procollagen gene expression could be prevented with SN50, a selective inhibitor of nuclear factor-kappaB activation, and superoxide dismutase, catalase, and tetramethylthiourea, scavengers of active oxygen species. AG1478, an inhibitor of epidermal growth factor receptor signaling, also prevented increased procollagen gene expression, but PD98059 and SB203580, inhibitors of mitogen-activated protein kinases, did not. These findings indicate that cigarette smoke can directly induce airway remodeling, specifically airway wall fibrosis, probably through active oxygen species-dependent transactivation of the epidermal growth factor receptor and subsequent nuclear factor-kappaB activation. Smoke-evoked inflammatory cells are not required for this process.
Wang
Rong D
RD
Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 Canada.
Tai
Hsin
H
Xie
Changshi
C
Wang
Xiaoshan
X
Wright
Joanne L
JL
Churg
Andrew
A
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis / Q000235:genetics; D011347:Procollagen / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects*; D014132:Trachea / Q000187:drug effects* / Q000473:pathology; D014133:Tracheal Diseases / Q000209:etiology / Q000473:pathology*
D011347:Procollagen; D012906:Smoke; D006909:Hydroxyproline