Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.
BACKGROUND
The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established.


OBJECTIVE
We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling.


METHODS
We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor-stimulated primary epithelial cells.


RESULTS
IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I.


CONCLUSIONS
Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I-stimulated airway epithelial cells during allergic inflammation.
Veraldi
Kristen L
KL
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Gibson
Bethany T
BT
Yasuoka
Hidekata
H
Myerburg
Michael M
MM
Kelly
Elizabeth A
EA
Balzar
Silvana
S
Jarjour
Nizar N
NN
Pilewski
Joseph M
JM
Wenzel
Sally E
SE
Feghali-Bostwick
Carol A
CA
D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index
D018972:Insulin-Like Growth Factor Binding Protein 3