Abstract
Vascular endothelial growth factor (VEGF) plays 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 stimulates VEGF expression. The IGF-binding proteins (IGFBPs), especially IGFBP-3, display distinctive properties and can interfere with various biological processes. In this study, an ovalbumin (OVA)-induced murine model of allergic airway disease was used to investigate which mechanism is implicated in the preventive and therapeutic actions of IGFBP-3 administered exogenously on allergen-induced bronchial inflammation and airway hyper-responsiveness, in particular focusing on the regulation of VEGF expression. Administration of recombinant human IGFBP-3 to OVA-inhaled mice substantially attenuated the increases in hypoxia-inducible factor (HIF)-α activity, IGF-I production, and VEGF protein levels in the lung. In addition, the blockade of IGF-I action decreased the OVA-induced VEGF expression, airway inflammation, and bronchial hyper-responsiveness. The administration of recombinant human IGFBP-3 or CBO-P11 also reduced significantly increases in inflammatory cells, airway hyper-responsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lung of OVA-inhaled mice. Moreover, when recombinant human IGFBP-3 was administered after the completion of OVA inhalation, these therapeutic effects of IGFBP-3 were also observed. These results indicate that IGFBP-3 administered exogenously may attenuate antigen-induced airway inflammation and hyper-responsiveness through the modulation of vascular leakage and VEGF expression mediated by HIF-1α/HIF-2α signaling as well as IGF-I action in allergic airway disease of mice.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.