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Recombinant IGFBP ‐3 inhibits allergic lung inflammation, VEGF production, and vascular leak in a mouse model of asthma
Author(s) -
Kim S. R.,
Lee K. S.,
Lee K. B.,
Lee Y. C.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2012.02837.x
Subject(s) - vascular endothelial growth factor , ovalbumin , medicine , vascular permeability , inflammation , immunology , growth factor , immunoglobulin e , vascular endothelial growth factor a , allergic inflammation , lung , sensitization , endocrinology , cancer research , antigen , receptor , vegf receptors , antibody
Background 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 ( IGFBP s), especially IGFBP ‐3, display distinctive properties and can interfere with various biological processes. Methods 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. Results 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. Conclusions 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.