Increased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD).
Tobacco smoke is believed to cause small airway disease and then chronic obstructive pulmonary disease (COPD), but the molecular mechanisms by which small airway obstruction occurs remain unknown. To study the gene expression levels of transforming growth factor (TGF)-beta1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD, we harvested highly pure samples of epithelial cells from small airways under direct vision by using an ultrathin bronchofiberscope BF-2.7T (outer diameter 2.7 mm with a biopsy channel of 0.8 mm in diameter). The expression levels of TGF-beta1 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA levels of TGF-beta1 corrected by beta-actin transcripts were significantly higher in the smoking group and patients with COPD than those in nonsmokers (p < 0.01). Furthermore, among smokers and patients with COPD, TGF-beta1 mRNA levels correlated positively with the extent of smoking history (pack-years) and the degree of small airway obstruction as assessed by measurements of flow-volume curves. Immunocytochemistry of the cells demonstrated more intense stainings for TGF-beta1 in samples from smokers and patients with COPD than from nonsmokers. Spontaneously released immunoreactive TGF-beta1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers. Our study showed a close link between smoking and expression of TGF-beta1 in small airways. Our results also suggested that small airway epithelial cells might be involved in obstructive changes found in smokers and patients with COPD.
Takizawa
H
H
Department of Laboratory Medicine and Respiratory Medicine, Tokyo University, School of Medicine, 7-3-1Hongo, Bunkyo-ku, Tokyo 113, Japan. TAKIZAWA-PHY@h.u-tokyo.ac.jp
Tanaka
M
M
Takami
K
K
Ohtoshi
T
T
Ito
K
K
Satoh
M
M
Okada
Y
Y
Yamasawa
F
F
Nakahara
K
K
Umeda
A
A
D000704:Analysis of Variance; D001706:Biopsy; D001980:Bronchi / Q000166:cytology*; D001999:Bronchoscopy; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005541:Forced Expiratory Volume; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008173:Lung Diseases, Obstructive / Q000145:classification / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000737:chemistry* / Q000254:growth & development; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D012907:Smoking / Q000276:immunology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics*; D014797:Vital Capacity
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta