Role of insulin-like growth factor binding protein-3 in allergic airway remodeling

Kristen L. Veraldi, Bethany T. Gibson, Hidekata Yasuoka, Michael M. Myerburg, Elizabeth A. Kelly, Silvana Balzar, Nizar N. Jarjour, Joseph M. Pilewski, Sally E. Wenzel, Carol A. Feghali-Bostwick

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Rationale: 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. Objectives: 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. Measurements and Main 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.

Original languageEnglish
Pages (from-to)611-617
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume180
Issue number7
DOIs
Publication statusPublished - 2009 Oct 1
Externally publishedYes

Fingerprint

Airway Remodeling
Insulin-Like Growth Factor Binding Protein 3
Asthma
Epithelium
Epithelial Cells
Bronchoalveolar Lavage Fluid
Conditioned Culture Medium
Insulin-Like Growth Factor I
Allergens
Inflammation
Insulin-Like Growth Factor Binding Proteins
Idiopathic Pulmonary Fibrosis
Airway Obstruction
Fluorescent Antibody Technique
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cytokines

Keywords

  • Asthma
  • Bronchoalveolar lavage
  • Fibrosis
  • Insulin-like growth factor binding protein
  • Primary epithelial cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Veraldi, K. L., Gibson, B. T., Yasuoka, H., Myerburg, M. M., Kelly, E. A., Balzar, S., ... Feghali-Bostwick, C. A. (2009). Role of insulin-like growth factor binding protein-3 in allergic airway remodeling. American Journal of Respiratory and Critical Care Medicine, 180(7), 611-617. https://doi.org/10.1164/rccm.200810-1555OC

Role of insulin-like growth factor binding protein-3 in allergic airway remodeling. / 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.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 180, No. 7, 01.10.2009, p. 611-617.

Research output: Contribution to journalArticle

Veraldi, KL, Gibson, BT, Yasuoka, H, Myerburg, MM, Kelly, EA, Balzar, S, Jarjour, NN, Pilewski, JM, Wenzel, SE & Feghali-Bostwick, CA 2009, 'Role of insulin-like growth factor binding protein-3 in allergic airway remodeling', American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 7, pp. 611-617. https://doi.org/10.1164/rccm.200810-1555OC
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. / Role of insulin-like growth factor binding protein-3 in allergic airway remodeling. In: American Journal of Respiratory and Critical Care Medicine. 2009 ; Vol. 180, No. 7. pp. 611-617.
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