Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression.
10.4168/aair.2016.8.2.161
- Author:
Wangjian ZHA
1
;
Mei SU
;
Mao HUANG
;
Jiankang CAI
;
Qiang DU
Author Information
1. Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
- Publication Type:In Vitro ; Original Article
- Keywords:
Asthma;
airway inflammation;
airway remodeling;
PEDF;
VEGF
- MeSH:
Airway Remodeling;
Animals;
Asthma;
Bronchoalveolar Lavage Fluid;
Collagen;
Eosinophils;
Epithelial Cells;
Goblet Cells;
Humans;
Hyperplasia;
Hypertrophy;
Inflammation*;
Lung;
Mice*;
Muscle, Smooth;
Ovalbumin;
Ovum;
Tail;
Vascular Endothelial Growth Factor A*;
Veins
- From:Allergy, Asthma & Immunology Research
2016;8(2):161-169
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells. METHODS: In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 microg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1beta. RESULTS: Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1beta stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1beta. CONCLUSIONS: These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma.
