The Effects of Recombinant IGFBP-3 on Allergen Induced VEGF Production and Vascular Leak in Asthmatic Inflammation
의약학 > 내과학
( Yong Chul Lee ) , ( So Ri Kim ) , ( Kyung Sun Lee ) , ( Yang Keun Rhee ) , ( Heung Bum Lee ) , ( Seoung Ju Park ) , ( Chi Ryang Chung ) , ( Seung Yong Park ) , ( Kyung Bae Lee )
대한결핵 및 호흡기학회
대한결핵및호흡기학회 추계학술발표초록집 2012년, 제114권 252(총1페이지)
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    Vascular endothelial growth factor (VEGF) plays as a pro-inflammatory mediator as well as a vascular permeability factor in bronchial asthma. The Insulin-like growth factor (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, focusing on regulation of VEGF expression. Recombinant human IGFBP-3 substantially attenuated the increases in hypoxia inducible factor (HIF)-a activity, IGF-I pro-duction, and VEGF protein levels in the lung of the mice. In addition, the blockade of IGF-I action decreased the OVA-induced VEGF expression, airway inflammation, and bronchial hyperresponsiveness. The administration of recombinant human IGFBP-3 or CBO-P11 also reduced significantly increases of inflammatory cells, airway hyper-responsiveness, levels of Th2 cytokines, and vascular permeability in the lung of OVA-inhaled mice. Moreover, when recombinant human IGFBP-3 was administered after completion of OVA inhalation, these therapeutic effects of IGFBP-3 were also observed. These results in-dicate that IGFBP-3 administered exogenously may attenuate antigen-induced airway inflammation and hyper-responsiveness through modulation of vascular leakage and VEGF expression mediated by HIF-1a/HIF-2a signaling as well as IGF-I action in allergic airway disease.
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