Role of Insulin-like Growth Factor Binding Protein-3 in Allergic Airway Remodeling

• Published in: American journal of respiratory and critical care medicine 2009-10, Vol.180 (7), p.611-617
• Main Authors: Veraldi, Kristen L, Gibson, Bethany T, Yasuoka, Hidekata, Myerburg, Michael M, Kelly, Elizabeth A, Balzar, Silvana, Jarjour, Nizar N, Pilewski, Joseph M, Wenzel, Sally E, Feghali-Bostwick, Carol A
• Format: Article
• Language: English
• Subjects: A. Asthma and Allergy; Adult; Allergens; Allergies; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asthma; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Biopsy; Blotting, Western; Bronchoalveolar Lavage Fluid - immunology; Bronchoscopy; Digestive system; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - immunology; Epithelial Cells - metabolism; Extracellular matrix; Female; Fibrosis; Fluorescent Antibody Technique; Humans; Inflammation; Insulin; Insulin-Like Growth Factor Binding Protein 3 - biosynthesis; Insulin-Like Growth Factor Binding Protein 3 - immunology; Insulin-like growth factors; Intensive care medicine; Investigative techniques, diagnostic techniques (general aspects); Lavage; Lung - immunology; Lung - metabolism; Lung - pathology; Male; Medical sciences; Middle Aged; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proteins; Pulmonary fibrosis; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - metabolism; Severity of Illness Index; Steroids
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200810-1555OC

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