Cigarette smoke inhibits human bronchial epithelial cell repair processes.
By interfering with the ability of airway epithelial cells to support repair processes, cigarette smoke could contribute to alterations of airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). The current study assessed the ability of cigarette smoke extract (CSE) to alter human airway epithelial cell chemotaxis, proliferation, and contraction of three-dimensional collagen gels, a model of extracellular matrix remodeling. The volatile components contained in cigarette smoke, acetaldehyde and acrolein, were able to inhibit all three processes. Nonvolatile components contained within lyophilized CSE also inhibited chemotaxis but displayed no activity in the other two bioassays. CSE also inhibited the ability of airway epithelial cells to release transforming growth factor (TGF)-beta and fibronectin. Exogenous fibronectin was unable to restore epithelial cell contraction of collagen gels. Exogenous TGF-beta partially restored the ability of airway epithelial cells to contract collagen gels and to produce fibronectin. This supports a role for inhibition of TGF-beta release in mediating the inhibitory effects of cigarette smoke. Taken together, the results of the current study suggest that epithelial cells present in the airways of smokers may be altered in their ability to support repair responses, which may contribute to architectural disruptions present in the airways in COPD associated with cigarette smoking.
Wang
H
H
Mount Sinai Hospital, Toronto, Ontario, Canada.
Liu
X
X
Umino
T
T
Sköld
C M
CM
Zhu
Y
Y
Kohyama
T
T
Spurzem
J R
JR
Romberger
D J
DJ
Rennard
S I
SI
D000079:Acetaldehyde / Q000494:pharmacology; D000171:Acrolein / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005591:Chemical Fractionation; D002633:Chemotaxis / Q000187:drug effects*; D003094:Collagen; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D005612:Freeze Drying; D005782:Gels; D006131:Growth Inhibitors / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014835:Volatilization
D005353:Fibronectins; D005782:Gels; D006131:Growth Inhibitors; D012906:Smoke; D016212:Transforming Growth Factor beta; D000171:Acrolein; D003094:Collagen; D000079:Acetaldehyde