Chest
Corticosteroid-Induced Apoptosis of Airway Epithelium*: A Potential Mechanism for Chronic Airway Epithelial Damage in Asthma
Section snippets
The Airway Epithelium Undergoes Apoptosis When Stimulated To Do So
The airway epithelium has death receptors and can undergo apoptosis when these receptors are stimulated. We have demonstrated the expression of the death receptor Fas and its ligand, FasL, in 1HAEoā cells, primary human bronchial epithelial cell in culture, and airway tissue sections from healthy human subjects.33 In additional experiments, we have demonstrated that airway epithelial cells in culture undergo apoptosis on the cross-ligation of Fas. This occurs in ā¤ 24 h, can approximate 30% of
CSs Elicit Apoptosis of the Airway Epithelium
With this in mind, we recently initiated a study36 to examine CS-induced apoptosis in the airway epithelium. We originally hypothesized that CSs would protect the airway epithelium from apoptotic stimuli. This hypothesis fit the available data, which suggested that CS therapy would aid in the restitution of a damaged airway epithelium37 without eliciting damage itself.35 To our surprise, CS treatment induced apoptosis in central airway epithelial cells. In both primary human airway epithelial
Conclusion
In summary, damage to the airway epithelium is an important pathologic event in patients with asthma, although demonstrating it by the currently available methods can be problematic. In addition to any derangements that may occur in the communication between the epithelium and underlying mesenchymal cells, and any damage that may be caused by inflammatory mediators and cells, we suggest that CSs may elicit apoptosis of the epithelium. Apoptosis is elicited in a concentration range similar to
ACKNOWLEDGMENT
I thank Kimm Hamann, PhD, Marcus Peter, PhD, and Charles Rudin, MD, at the University of Chicago for their advice. I thank Bertha Marroquin and Kimberly Wojcik for their many years of technical assistance.
References (53)
- et al.
Remodeling of asthmatic airways by glucocorticosteroids
J Allergy Clin Immunol
(1996) - et al.
Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission
Chest
(1990) - et al.
A targeted glucocorticoid receptor antisense transgene increases thymocyte apoptosis and alters thymocyte development
Immunity
(1995) - et al.
Arnebin-1 accelerates normal and hydrocortisone-induced impaired wound healing
J Invest Dermatol
(1999) - et al.
Proliferation and activation of bronchial epithelial cells in corticosteroid-dependent asthma
J Allergy Clin Immunol
(2001) - et al.
An in vitro comparison of commonly used topical glucocorticoid preparations
J Allergy Clin Immunol
(1999) - et al.
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC)
Cell
(1996) - et al.
An APAF-1-cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9
J Biol Chem
(1999) - et al.
Damage of the airway epithelium and bronchial reactivity in patients with asthma
Am Rev Respir Dis
(1985) - et al.
Cellular events in the bronchi in mild asthma and after bronchial provocation
Am Rev Respir Dis
(1989)
Bronchial biopsies in asthma: an ultrastructural, quantitative study and correlation with hyperreactivity
Am Rev Respir Dis
Airway inflammation in mild intermittent and in persistent asthma
Am J Respir Crit Care Med
Airway mucosal inflammation even in patients with newly diagnosed asthma
Am Rev Respir Dis
Cell proliferation in the bronchial mucosa of asthmatics and chronic bronchitis
Am J Respir Crit Care Med
Ciliated cell damage in the bronchial epithelium of asthmatics and non-asthmatics
Clin Exp Allergy
The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects
Thorax
Epithelial desquamation in asthma: artifact or pathology?
Am J Respir Crit Care Med
Expression of CD44 isoforms is increased in the airway epithelium of asthmatic subjects
Am J Respir Cell Mol Biol
The involvement of the epidermal growth factor receptor in epithelial repair in asthma
FASEB J
The epidermal growth factor receptor and its ligand family: their potential role in repair and remodeling in asthma
Allergy
Asthma from bronchoconstriction to airways inflammation and remodeling
Am J Respir Crit Care Med
Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes
J Immunol
Rapid in vivo effects of glucocorticoids on the integrity of rat lymphocyte genomic deoxyribonucleic acid
Endocrinology
Efficacy and safety of inhaled corticosteroids in asthma
Am Rev Respir Dis
The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation
Am J Respir Crit Care Med
Current issues for establishing inhaled corticosteroids as the antiinflammatory agents of choice in asthma
J Allergy Clin Immunol
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This research was supported by grants HL-60531 and HL-63300 from the National Heart, Lung, and Blood Institute, and by grant CIHR 43898 from the Canadian Institute of Health Research.