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Intrinsic Phenotypic Differences of Asthmatic Epithelium and Its Inflammatory Responses to Respiratory Syncytial Virus and Air Pollution
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 45:1090-1100
- Publication Year :
- 2011
- Publisher :
- American Thoracic Society, 2011.
-
Abstract
- A substantial proportion of healthcare cost associated with asthma is attributable to exacerbations of the disease. Within the airway, the epithelium forms the mucosal immune barrier, the first structural cell defense against common environmental insults such as respiratory syncytial virus (RSV) and particulate matter. We sought to characterize the phenotype of differentiated asthmatic-derived airway epithelial cultures and their intrinsic inflammatory responses to environmental challenges. Air-liquid interface (ALI) cultures were generated from asthmatic (n = 6) and nonasthmatic (n = 6) airway epithelial cells. Airway tissue and ALI cultures were analyzed by immunohistochemistry for cytokeratin-5, E-cadherin, Ki67, Muc5AC, NF-κB, the activation of p38, and apoptosis. ALI cultures were exposed to RSV (4 × 10(6) plaque forming unit/ml), particulate matter collected by Environmental Health Canada (EHC-93, 100 μg/ml), or mechanically wounded for 24, 48, and 96 hours and basolateral supernatants analyzed for inflammatory cytokines, using Luminex and ELISA. The airway epithelium in airway sections of patients with asthma as well as in vitro ALI cultures demonstrated a less differentiated epithelium, characterized by elevated numbers of basal cells marked by the expression of cytokeratin-5, increased phosphorylation of p38 mitogen-activated protein kinase, and less adherens junction protein E-cadherin. Transepithelial resistance was not different between asthmatic and nonasthmatic cultures. In response to infection with RSV, exposure to EHC-93, or mechanical wounding, asthmatic ALI cultures released greater concentrations of IL-6, IL-8, and granulocyte macrophage colony-stimulating factor, compared with nonasthmatic cultures (P < 0.05). This parallel ex vivo and in vitro study of the asthmatic epithelium demonstrates an intrinsically altered phenotype and aberrant inflammatory response to common environmental challenges, compared with nonasthmatic epithelium.
- Subjects :
- Adult
Male
Pulmonary and Respiratory Medicine
Clinical Biochemistry
Apoptosis
Respiratory Mucosa
Mucin 5AC
Granulocyte
p38 Mitogen-Activated Protein Kinases
Proinflammatory cytokine
Young Adult
Air Pollution
medicine
Humans
Macrophage
Phosphorylation
Respiratory system
Child
Molecular Biology
Cells, Cultured
Plaque-forming unit
business.industry
NF-kappa B
Cell Biology
respiratory system
Cadherins
Asthma
Epithelium
Respiratory Syncytial Viruses
respiratory tract diseases
Ki-67 Antigen
medicine.anatomical_structure
Child, Preschool
Immunology
Cytokines
Keratin-5
Respiratory epithelium
Female
Particulate Matter
business
Ex vivo
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....c73ebdf3f3059e2ff337710118343342