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

Abstract

To study the inflammatory responses of small-airway epithelium in smokers, we harvested enough living epithelial cells (1.97 x 10(6) +/- 0.74 x 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 beta-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 x 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.

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

“…The increased numbers of both CD8+ T-cells and monocytes/macrophages in the lungs of COPD patients [1,2] in combination with the increased expression of TGF-β and its correlation to the number of intraepithelial macrophages [16,17] merits a closer study of this particular intra epithelial T-cell population. In fact, it still has to be established whether the presence of these cells is beneficial or detrimental to the disease.…”

“…This is in line with studies showing that the production of TGF-β in the microenvironment within the epithelium in vivo is necessary to maintain the αEβ7 expression on IELs [15] . Interestingly, the airway epithelium of both smokers and COPD patients has been shown to express elevated levels of TGF-β 1 [16,17] . Therefore, we hypothesis that the lung of COPD patients, withholding high levels of TGF-β and large numbers of macrophages, provides a good environment for differentiation of recruited CD8+ T-cells to become αEβ7 expressing cells.…”

Lack of Association of a Common Polymorphism in the 3'-UTR of Interleukin 8 with Non Small Cell Lung Cancer in Kashmir

“…Elevated number of inflammatory cells and higher levels of pro inflammatory cytokines are seen in the tumor micrenvironment and their surrounding stromal tissues (Takizawa et al, 2000;Balkwill, 2001). The increased risk of lung cancer in patients with chronic inflammatory diseases such as chronic obstructive pulmonary disease, asthma, and chronic interstitial lung fibrosis have been observed (Cohen et al, 1997;Mayne et al, 1999;Boffett et al, 2001).…”

Update on the roles of distal airways in COPD

“…MUC5AC and MUC5B [26]) from hyperplastic goblet cells probably contributes to lumen obstruction by muco-inflammatory exudates [8]. Finally, small airway epithelium may promote the recruitment of neutrophils, macrophages and T lymphocytes via the secretion of specific chemoattractants [30][31][32][33].…”