Capital Medical University, Beijing, China
Copyright 2016, American College of Chest Physicians. All Rights Reserved.
SESSION TITLE: Asthma II
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM
PURPOSE: It is well known that IL-25 plays important role in the pathogenesis of asthma. We have previously shown that nasal challenge with IL-25 causes the airways accumulation of eosinophils, collagen deposition, mucus secretion and angiogenesis and other changes of airway remodelling in mice. In vitro, IL-25 induces expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) by human umbilical vein endothelial cells (HUVEC), which is possibly through PI3K signalling pathway because a pan PI3K inhibitor LY294002 abolishes IL-25-induced angiogenesis. In the present study, we hypothesized that PI3K inhibitor LY294002 is able to reduce IL-25-induced asthma-like airways inflammation, allergen-independent airway hyperresponsiveness (AHR) and airways remodelling in vivo.
METHODS: 8-10 week old female BALB / c mice were intranasally changed with recombinant murine IL-25 with or without PI3K inhibitor LY294002. Nasal challenge with DMSO was used as vehicle control. Lung tissues were taken at experimental acute, subacute, chronic and convalescent phases and embedded in paraffin. Periodic acid-Schiff (PAS) and Masson’s trichrome methods were employed for measuring mucus secretion and collagen deposition in lung sections. Immunohistochemistry for α-sooth muscle actin (α-SMA) and CD31 was used for measuring changes of smooth muscle hypertrophy and angiogenesis.
RESULTS: Compared with the control group, LY294002 significantly reduced IL-25-induced airways infiltration of inflammatory cells, AHR, total collagen content in lung tissues and collagen deposition surrounding bronchial wall and blood vessels, mucus secretion, as well as airway inhibited smooth muscle hypertrophy and angiogenesis.
CONCLUSIONS: Pan-PI3K inhibitor LY294002 is not only able to inhibit IL-25-induced asthma-like airways inflammation, but also abolish AHR and allergen-independent airway remodelling.
CLINICAL IMPLICATIONS: Our data suggest that targeting PI3K signalling might be benefit for treatment of asthma.
DISCLOSURE: The following authors have nothing to disclose: Ping Huang, Yan Li, Zhe Lv, Jingjing Wang, Yafei Chi, Qian Zhan, Xiujuan Yao, Chris Corrigan, Kewu Huang, Wei Wang, Sun Ying
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