title: Activation of bronchial epithelial cells in smokers without airway obstruction and patients with COPD.
abstract: 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.
  
  
  METHODS
  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-alpha 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Bereich Pneumologie, Klinikum der Universität Regensburg, Regensburg, Germany. christian.schulz@klinik.uni-regensburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krätzel
authors.forename: Konrad
authors.initials: K
authors.lastname: Wolf
authors.forename: Stephan
authors.initials: S
authors.lastname: Schroll
authors.forename: Martina
authors.initials: M
authors.lastname: Köhler
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeifer
mesh_terms: D001980:Bronchi / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D018925:Chemokines / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012907:Smoking / Q000276:immunology*
chemical_list: D018925:Chemokines; D012333:RNA, Messenger