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Clinical Investigations: COPD |

Activation of Bronchial Epithelial Cells in Smokers Without Airway Obstruction and Patients With COPD*

Christian Schulz, MD; Kirsten Krätzel; Konrad Wolf, PhD; Stephan Schroll, MD; Martina Köhler; Michael Pfeifer, MD
Author and Funding Information

*From the Klinik und Poliklinik für Innere Medizin II, Bereich Pneumologie (Drs. Schulz, Wolf, and Schroll, and Ms. Krätzel, and Ms. Köhler), Klinikum der Universität Regensburg, Regensburg; and Klinik Donaustauf (Dr. Pfeifer), Donaustauf, Germany.

Correspondence to: Christian Schulz, MD, Medizinische Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; e-mail: christian.schulz@klinik.uni-regensburg.de



Chest. 2004;125(5):1706-1713. doi:10.1378/chest.125.5.1706
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Study objective: The aim of this study was to investigate the basal level as well as the tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced expression and release of the neutrophil chemoattractants interleukin (IL)-8 and growth-related oncogene (GRO)-α in primary bronchial epithelial cells (PBECs) from smokers without airflow obstruction and patients with COPD. In addition, the expression of both TNF-α-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-γ 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-α were not significantly different between both groups, although a trend toward higher IL-8 levels was seen in patients with COPD. TNF-α induced significantly higher mRNA amounts of IL-8 (p = 0.005) and GRO-α (p = 0.007) in patients with COPD. This was accompanied by higher protein release data for IL-8 (p = 0.005) and GRO-α (p = 0.007). IFN-γ had no significant effect on the mRNA expression and protein release of IL-8 and GRO-α 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-α-receptor subtypes.

Conclusion: PBECs from patients with COPD show significantly higher TNF-α-induced release of the neutrophil chemoattractant CXC-chemokines IL-8 and GRO-α 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.

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