TY - JOUR
T1 - Airway epithelial cells from asthmatic children differentially express proremodeling factors
AU - Lopez-Guisa, Jesus M.
AU - Powers, Claire
AU - File, Daniele
AU - Cochrane, Elizabeth
AU - Jimenez, Nathalia
AU - Debley, Jason S.
N1 - Funding Information:
Supported by American Lung Association Biomedical grant RG-71839-N (PI: J.S.D.) and National Heart, Lung, and Blood Institute grant K23HL077626 (PI: J.S.D.).
Funding Information:
Disclosure of potential conflict of interest: J. S. Debley receives research support from the American Lung Association and the National Institutes of Health/National Heart, Lung, and Blood Institute . The rest of the authors declare that they have no relevant conflicts of interest.
PY - 2012/4
Y1 - 2012/4
N2 - Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.
AB - Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.
KW - Asthma
KW - TGF-β2
KW - a disintegrin and metalloprotease 33
KW - airway remodeling
KW - children
KW - epithelial cells vascular endothelial growth factor
KW - periostin
UR - http://www.scopus.com/inward/record.url?scp=84859128562&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2011.11.035
DO - 10.1016/j.jaci.2011.11.035
M3 - Article
AN - SCOPUS:84859128562
SN - 0091-6749
VL - 129
SP - 990-997.e6
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -