Phosphoinositide 3-kinase-delta inhibitor reduces vascular permeability in a murine model of asthma.

Lee KS ，Park SJ ，Kim SR ，Min KH ，Jin SM ，Puri KD ，Lee YC ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

Inhibition of phosphoinositide 3-kinase delta attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model.

Lee KS ，Lee HK ，Hayflick JS ，Lee YC ，Puri KD ... -  《-》

HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium.

Kim SR ，Lee KS ，Park HS ，Park SJ ，Min KH ，Moon H ，Puri KD ，Lee YC ... -  《-》

Recombinant IGFBP-3 inhibits allergic lung inflammation, VEGF production, and vascular leak in a mouse model of asthma.

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.

Kim SR ，Lee KS ，Lee KB ，Lee YC ... -  《-》

Mast cells can mediate vascular permeability through regulation of the PI3K-HIF-1alpha-VEGF axis.

Lee KS ，Kim SR ，Park SJ ，Min KH ，Lee KY ，Choe YH ，Park SY ，Chai OH ，Zhang X ，Song CH ，Lee YC ... -  《-》