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 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).


CONCLUSIONS
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.
Vignola
A M
AM
Istituto di Fisiopatologia Respiratoria, CNR, Palermo, Italy.
Chiappara
G
G
Siena
L
L
Bruno
A
A
Gagliardo
R
R
Merendino
A M
AM
Polla
B S
BS
Arrigo
A P
AP
Bonsignore
G
G
Bousquet
J
J
Chanez
P
P
D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000166:cytology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology*
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D019013:CD40 Antigens; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D023201:CD40 Ligand