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

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 s...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2001-11, Vol.108 (5), p.738-746
Main Authors: Vignola, Antonio Maurizio, Chiappara, Giuseppina, Siena, Liboria, Bruno, Andreina, Gagliardo, Rosalia, Merendino, Anna Maria, Polla, Barbara S., Arrigo, A.Patrik, Bonsignore, Giovanni, Bousquet, Jean, Chanez, Pascal
Format: Article
Language:English
Subjects:
Administration, Inhalation
Administration, Oral
Adrenal Cortex Hormones - administration & dosage
Adrenal Cortex Hormones - therapeutic use
Adult
Aged
Allergic diseases
Anti-Asthmatic Agents - administration & dosage
Anti-Asthmatic Agents - therapeutic use
Apoptosis
Asthma
Asthma - drug therapy
Asthma - metabolism
Asthma - pathology
Biological and medical sciences
Biomarkers - analysis
Bronchi - cytology
CD40 Antigens - immunology
CD40 Antigens - metabolism
CD40 Ligand - immunology
CD40 Ligand - metabolism
Cell Division
corticosteroids
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Humans
Immunohistochemistry
Immunopathology
In Situ Nick-End Labeling
inflammation
Male
Medical sciences
Middle Aged
NF-kappa B - metabolism
Proliferating Cell Nuclear Antigen - immunology
Proliferating Cell Nuclear Antigen - metabolism
proliferation
Respiratory and ent allergic diseases
Respiratory Mucosa - metabolism
Respiratory Mucosa - pathology
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Summary: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 (NFκB 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, NFκB, 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. (J Allergy Clin Immunol 2001;108:738-46.)
ISSN:0091-6749
1097-6825
DOI:10.1067/mai.2001.119160