Airway epithelial cells from asthmatic children differentially express proremodeling factors

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 4; pp. 990 - 997.e6
• Main Authors: Lopez-Guisa, Jesus M., Powers, Claire, File, Daniele, Cochrane, Elizabeth, Jimenez, Nathalia, Debley, Jason S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2012; Elsevier; Elsevier Limited
• Subjects: a disintegrin and metalloprotease 33; ADAM Proteins - genetics; ADAM Proteins - metabolism; Adolescent; adults; Age; Airway Remodeling; Algorithms; Allergy and Immunology; Anesthesia; Angiogenesis; Asthma; Asthma - genetics; Asthma - metabolism; Atopy; Biological and medical sciences; Biopsy; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell culture; Cells, Cultured; Child; childhood; Children; Children & youth; Chronic obstructive pulmonary disease, asthma; Cytokines; Data processing; Differentiation; Efficiency; Enzyme-linked immunosorbent assay; Epithelial cells; Epithelial Cells - metabolism; epithelial cells vascular endothelial growth factor; Epithelium; Family medical history; Female; Fibroblast growth factor 2; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; gene expression regulation; Humans; Immunopathology; Interleukin 13; Interleukin 4; Lung; lung function; Male; Medical sciences; Metalloproteinase; metalloproteinases; nose; patients; Pediatrics; periostin; Pneumology; Polymerase chain reaction; Proteins; quantitative polymerase chain reaction; Respiratory Mucosa - metabolism; Respiratory tract; RNA; RNA, Messenger - metabolism; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Software; Studies; TGF-β2; transforming growth factor beta 2; Transforming Growth Factor beta2 - metabolism; Transforming growth factor- beta; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; vascular endothelial growth factors; ATS; Feno; periostin; VEGF; airway remodeling; ADAM33; FEF25-75; Asthma; epithelial cells vascular endothelial growth factor; Ct; children; BEGM; a disintegrin and metalloprotease 33; ICS; TGF-β2; GAPDH; ALI; AEC; Vascular epithelial growth factor; Fraction of exhaled nitric oxide; Airway epithelial cell; F eno; Inhaled corticosteroid; Air-liquid interface; American Thoracic Society; Cycle threshold; Glyceraldehyde-3-phosphate dehydrogenase; Forced expiratory flow between 25% and 75% of expiration; Bronchial epithelial growth medium; FEF 25-75; Human; Cell proliferation; Lung disease; Immunopathology; Disintegrin; Respiratory disease; Remodeling; Respiratory system; Respiratory tract; Vascular endothelium growth factor; Immunology; Periostin; Transforming growth factor β2; Bronchus disease; Epithelial cell; Obstructive pulmonary disease; Child; Tumor suppressor gene
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.11.035

The airway epithelium can express factors that drive subepithelial airway remodeling. TGF-β2, vascular epithelial growth factor (VEGF), a disintegrin and metalloprotease 33 (ADAM33), and periostin are hypothesized to be involved in subepithelial remodeling and are overexpressed in adult asthmatic airways. Epidemiologic data suggest that lung function deficits in asthmatic patients are acquired in childhood. We sought to determine whether airway epithelial cells (AECs) from asthmatic children differentially express TGF-β2, VEGF, ADAM33, or periostin compared with cells from atopic nonasthmatic and healthy children intrinsically or in response to IL-4/IL-13 stimulation. Bronchial and nasal epithelial cells were obtained from brushings from well-characterized asthmatic (n = 16), atopic nonasthmatic (n = 9), and healthy (n = 15) children after achievement of anesthesia for elective procedures. After differentiation at an air-liquid interface (ALI) for 3 weeks, conditioned media were sampled and RNA was extracted from unstimulated and IL-4/IL-13–stimulated cultures. TGF-β2 and VEGF levels were measured with ELISA. ADAM33 and periostin expression was assessed by using real-time PCR. TGF-β2 and VEGF production was significantly greater in bronchial and nasal ALI cultures from asthmatic children than in cultures from atopic nonasthmatic and healthy children. TGF-β2 levels increased significantly in asthmatic cultures after IL-4/IL-13 stimulation. Within-subject correlation between nasal and bronchial ALI production of TGF-β2 (r = 0.64, P = .001) and VEGF (r = 0.73, P < .001) was good. Periostin expression was 3.7-fold higher in bronchial cells (P < .001) and 3.9-fold higher in nasal cells (P < .004) from asthmatic children than in cells from atopic nonasthmatic or healthy children. ADAM33 was not differentially expressed by AECs from asthmatic patients compared with that from cells from atopic nonasthmatic or healthy children. AECs from asthmatic children differentially express TGF-β2, VEGF, and periostin compared with cells from atopic nonasthmatic and healthy children. Nasal epithelial cells might be a suitable surrogate for bronchial cells that could facilitate investigation of the airway epithelium in future longitudinal pediatric studies.