507 The Protective Effects of Exogenous IGFBP-3 on Allergic Airway Inflammation through Blockade of vegf Production

BACKGROUND: Bronchial asthma is a chronic airway inflammatory disease that is usually accompanied by increased vascular leakage, resulting in plasma exudation. Vascular endothelial growth factor (VEGF) plays as a pro-inflammatory mediator as well as a vascular permeability factor in bronchial asthma. Insulin-like growth factor (IGF)-I is also involved in the inflammatory process associated with bronchial asthma and it has been demonstrated to stimulate VEGF expression. The IGF binding proteins (IGFBPs) are a complex family of proteins which bind IGFs with high affinity. IGFBPs, especially IGFBP-3, display distinctive properties and can interfere with various biological processes. However, there are little data on the effect and the molecular basis of IGFBP-3 on allergen-induced bronchial inflammation and airway hyper-responsiveness. METHODS: This study was aimed to investigate the related signaling regarding the action of IGFBP-3 on bronchial inflammation and airway hyper-responsiveness in allergic airway disease of mice. RESULTS: In this study with an ovalbumin (OVA)-induced murine model of allergic airway disease, the increases of HIF-1a/HIF-2a activity and VEGF protein levels in lungs after OVA inhalation were blocked substantially by the administration of IGFBP-3. We also showed that the increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, and increased levels of IL-4, IL-5, IL-13, and vascular permeability in lungs after OVA inhalation were significantly reduced by the administration of IGFBP-3. CONCLUSIONS: These results indicate that IGFBP-3 may attenuate antigen-induced airway inflammation and hyper-responsiveness through the modulation of vascular leakage and VEGF expression mediated by HIF-1a/HIF-2a in allergic airway disease of mice.