Increased expression of inflammatory mediators in small-airway epithelium from tobacco smokers

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 278; no. 5; pp. 906 - L913
• Main Authors: Takizawa, Hajime, Tanaka, Mitsuru, Takami, Kazutaka, Ohtoshi, Takayuki, Ito, Koji, Satoh, Masaru, Okada, Yasumasa, Yamasawa, Fumihiro, Umeda, Akira
• Format: Journal Article
• Language: English
• Published: United States 01.05.2000
• Subjects: Biopsy; Bronchi - drug effects; Bronchi - immunology; Bronchi - pathology; Bronchoscopy; Cell Count; Cell Survival - immunology; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Female; Gene Expression - drug effects; Gene Expression - immunology; Humans; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Intercellular Adhesion Molecule-1 - genetics; Interleukin-8 - genetics; Interleukin-8 - immunology; Male; Middle Aged; Pneumonia - chemically induced; Pneumonia - immunology; Pneumonia - pathology; Respiratory Function Tests; Respiratory Mucosa - immunology; Respiratory Mucosa - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Smoking - adverse effects
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2000.278.5.l906

1  Department of Laboratory Medicine and Respiratory Medicine, School of Medicine, Tokyo University, Bunkyo-ku, Tokyo 113; and 2  World Health Organization Collaborating Centre, Tokyo Medical College, Shinjuku-ku; and 3  Department of Diagnostic Radiology, School of Medicine, Keio University, Tokyo 160, Japan To study the inflammatory responses of small-airway epithelium in smokers, we harvested enough living epithelial cells (1.97   × 10 6  ± 0.74 × 10 6 ) with a new ultrathin fiberscope from the very peripheral airways of 22 current smokers and 17 subjects who never smoked after informed consent was obtained. The cells were keratin positive and composed mainly of nonciliated cells. The expression levels of inflammatory markers [interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1] were evaluated with RT-PCR. The magnitude of the mRNA levels corrected by -actin transcripts of IL-8 and ICAM-1 was significantly higher in the smokers than in the nonsmokers ( P   < 0.001). Furthermore, among current smokers, IL-8 mRNA levels correlated positively with the extent of smoking history [in pack · years (packs/day × no. of years of smoking); r  = 0.754,  P  <   0.001]. Spontaneously released IL-8 and soluble ICAM-1 levels ( n  = 12) from cultured epithelial cells were elevated in subjects with a smoking history than in those without it (IL-8, 1,580 ±   29.6 vs. 354 ± 39.4 pg · 10 6 cells 1 · 24 h 1 ; P  < 0.001; soluble ICAM-1, 356.0 ± 45.9 vs. 112.9 ± 12.9 pg · 10 6 cells 1 · 24 h 1 ; P  < 0.01 by Student's t -test ). In contrast, the epithelial cells from the main bronchi did not show such differences between smokers and nonsmokers. Our study highlighted a close link between smoking and the expression of inflammatory mediators such as IL-8 and ICAM-1 in small airways. Our results also suggested that this new ultrathin bronchofiberscope promised a good approach for the evaluation of cellular changes in the small airways. smoking; interleukin-8; intercellular adhesion molecule-1; peripheral airways