کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3202990 1201984 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphoinositide 3-kinase-δ inhibitor reduces vascular permeability in a murine model of asthma
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Phosphoinositide 3-kinase-δ inhibitor reduces vascular permeability in a murine model of asthma
چکیده انگلیسی

BackgroundBronchial asthma is characterized by inflammation of the airways, which is usually accompanied by increased vascular permeability, resulting in plasma exudation. Vascular endothelial growth factor (VEGF) has been implicated in contributing to asthmatic tissue edema through its effect on vascular permeability. Many cellular responses of VEGF are regulated by the lipid products of phosphoinositide 3-kinase (PI3K). However, the effect of PI3K catalytic subunit p110δ on VEGF-mediated signaling is unknown. Recently, an isoform-specific small molecule inhibitor, IC87114, which is selective for p110δ catalytic activity, has been identified.ObjectiveWe have sought to investigate the role of PI3K-δ, more specifically in the increase of vascular permeability.MethodsFemale BALB/c mice were sensitized and challenged with ovalbumin. We have investigated the effect of IC87114 on airway inflammation, TH2 cytokines expression, airway hyperresponsiveness, plasma extravasation, hypoxia-inducible factor 1α expression, and VEGF expression in a murine model of asthma.ResultsOur current study has revealed that IC87114 reduces antigen-induced airway infiltration of inflammatory cells, secretion of TH2 cytokines in lungs, airway hyperresponsiveness, and vascular permeability. Moreover, we have found that inhibition of p110δ reduces ovalbumin-induced upregulation of VEGF level.ConclusionThese results suggest that PI3K-δ inhibitor attenuates antigen-induced airway inflammation and hyperresponsiveness by preventing vascular leakage in mice.Clinical implicationsThese findings provide a crucial molecular mechanism for the potential role of PI3K-δ in asthma and other airway inflammatory disorders.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Allergy and Clinical Immunology - Volume 118, Issue 2, August 2006, Pages 403–409
نویسندگان
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