Activation of bronchial epithelial cells in smokers without airway obstruction and patients with COPD

Study objective: The aim of this study was to investigate the basal level as well as the tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma-induced expression and release of the neutrophil chemoattractants interleukin (IL)-8 and growth-related oncogene (GRO)-alpha in primary bronchial epithelial cells (PBECs) from smokers without airflow obstruction and patients with COPD. In addition, the expression of both TNF-alpha-receptor subtypes-p55 TNF-receptor subtype (TNF-R55) and p75 TNF-receptor subtype (TNF-R75)-was quantified in PBECs. Design: PBECs from eight smokers without airflow limitation and eight patients with COPD were stimulated with 50 ng/mL of TNF and 200 U/mL of IFN-gamma for 4 h along with unstimulated time controls. The transcriptional expression and protein release were quantitatively assessed by means of real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Basal level messenger RNA (mRNA) expression and protein release of IL-8 and GRO-alpha were not significantly different between both groups, although a trend toward higher IL-8 levels was seen in patients with COPD. TNF-alpha induced significantly higher mRNA amounts of IL-8 (p = 0.005) and GRO-alpha (p = 0.007) in patients with COPD. This was accompanied by higher protein release data for IL-8 (p = 0.005) and GRO-alpha (p = 0.007). IFN-gamma had no significant effect on the mRNA expression and protein release of IL-8 and GRO-a in either group. TNF-R55 and TNF-R75 were detectable in PBECs. However, no significant differences were found between both groups with respect to steady-state mRNA levels of TNF-alpha-receptor subtypes. Conclusion: PBECs from patients with COPD show significantly higher TNF-alpha-induced release of the neutrophil chemoattractant CXC-chemokines IL-8 and GRO-alpha compared to smokers without airflow limitation. This increased activation of PBECs may contribute to the predominance of neutrophils seen in the airway lumen of patients with COPD.