Proliferation and activation of bronchial epithelial cells in corticosteroid-dependent asthma

J Allergy Clin Immunol. 2001 Nov;108(5):738-46. doi: 10.1067/mai.2001.119160.


Background: Structural and functional characteristics of bronchial epithelial cells in corticosteroid-dependent asthma are unknown.

Objective: In bronchial biopsy specimens from 16 control, 9 untreated asthmatic, 9 inhaled corticosteroid-treated asthmatic, and 19 corticosteroid-dependent asthmatic subjects, we evaluated epithelium morphology and patterns of cell apoptosis, proliferation, and activation.

Methods: We used the terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) technique to study apoptosis. Immunohistochemistry was used to evaluate the expression of molecules related to apoptosis (such as Bcl-2 and P53), cell proliferation (PCNA), and cell activation (NFkappaB and CD40/CD40-L).

Results: Epithelium thickness was higher in corticosteroid-dependent asthmatic and control subjects than in inhaled corticosteroid-treated and untreated asthmatic subjects (P < .0001 and P <.0003). Very few TUNEL-positive epithelial cells were found in the 4 groups. Bcl-2 expression was higher in all groups of asthmatic subjects than in controls (P < .001). In corticosteroid-dependent asthmatic subjects, PCNA, NFkappaB, and CD40-L expression was higher than in inhaled corticosteroid-treated asthmatic (P < .001), untreated asthmatic (P <.001 and P < .04), and control (P < .01) subjects. CD40 expression was greater in corticosteroid-dependent asthmatic and untreated asthmatic subjects than in inhaled corticosteroid-treated asthmatic subjects (P < .0001 and P < .0006) and controls (P < .02 and P < .03). In corticosteroid-dependent asthma, PCNA expression was correlated with the epithelium thickness (P < .007).

Conclusion: This study shows that in bronchial epithelial cells of corticosteroid-dependent asthma, markers of cell survival and proliferation are coexpressed with markers of cell activation, suggesting that in this disease epithelium repair is associated with a persistent activation state of epithelial cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / therapeutic use*
  • Apoptosis
  • Asthma / drug therapy
  • Asthma / metabolism*
  • Asthma / pathology*
  • Biomarkers / analysis
  • Bronchi / cytology*
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Cell Division
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Proliferating Cell Nuclear Antigen / immunology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology*


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Biomarkers
  • CD40 Antigens
  • NF-kappa B
  • Proliferating Cell Nuclear Antigen
  • CD40 Ligand