Expression and Release of Interleukin-8 by Human Bronchial Epithelial Cells from Patients with Chronic Obstructive Pulmonary Disease, Smokers, and Never-Smokers

Abstract

BACKGROUND: One of the consistently observed features in chronic obstructive pulmonary disease (COPD) are markedly increased neutrophils in the airways which are accompanied by increased levels of interleukin-8 (IL-8) in induced sputum and bronchoalveolar lavage fluid. To some extent, IL-8 may derive from bronchial epithelial cells since airway epithelium plays a crucial role in initiating and augmenting host defense mechanisms. OBJECTIVES: We hypothesized that a marked increase in bronchoepithelial IL-8 expression and release may be found in the airway epithelium of COPD patients compared to 'healthy' smokers and never-smokers. METHODS: Primary bronchoepithelial cell cultures from COPD patients, smokers, and never-smokers were established. The unstimulated and TNFalpha-induced IL-8 release was measured by enzyme-linked immunosorbent assay. In addition, mRNA expression levels were quantified by means of reverse transcriptase polymerase chain reaction and light cycler measurements. RESULTS: In subjects with COPD the constitutive and stimulated IL-8 release was significantly higher compared to 'healthy' smokers and control subjects, whereas no differences were seen between smokers and the control group. Quantitative assessment of transcript levels confirmed these data, displaying significantly higher mRNA levels in primary bronchial epithelial cells from COPD patients compared to controls (p < 0.05) in uninduced and stimulated conditions (p < 0.05). CONCLUSIONS: These results suggest that patients with chronic obstructive airflow limitation are characterized by a significant upregulation of bronchial epithelial IL-8 expression levels and secretion, indicating specific differences in epithelial cell activation in COPD patients compared to smokers and control subjects.