Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma.

Abstract

BACKGROUND:

Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. Peroxisome proliferator-activated receptors (PPARs) were reported to regulate inflammatory responses in many cells. In this study we examined the effect of a PPAR-gamma agonist on the airway smooth muscle and the production of transforming growth factor (TGF)-beta1 and vascular endothelial growth factor (VEGF).

METHODS:

We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with ciglitazone during OVA challenge.

RESULTS:

Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR to methacholine compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of ciglitazone intranasally significantly inhibited the development of AHR, eosinophilic inflammation, and importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. However, intranasal ciglitazone treatment did not reduce the level of TGF-beta1 and VEGF in bronchoalveolar lavage fluid.

CONCLUSIONS:

These results suggest that intranasal administration of ciglitazone can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. The mechanism might not be related to VEGF and TGF production. Further study is needed.

• Authors: Chin Kook Rhee, Sook Young Lee, Ji Young Kang, Seung Joon Kim, Soon Suk Kwon, Young Kyoon Kim, Sung Hak Park
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 148 Issue 4 Pg. 289-96 ( 2009) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 19001788 (Publication Type: Journal Article)
• Copyright: Copyright 2008 S. Karger AG, Basel.

Chemical References

• Anti-Asthmatic Agents
• PPAR gamma
• Thiazolidinediones
• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Ovalbumin
• ciglitazone

Topics

• Administration, Intranasal
• Animals
• Anti-Asthmatic Agents (administration & dosage, pharmacology, therapeutic use)
• Asthma (drug therapy, pathology, physiopathology)
• Bronchi (drug effects, pathology)
• Bronchial Provocation Tests
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cell Count
• Disease Models, Animal
• Eosinophils (cytology)
• Female
• Mice
• Mice, Inbred BALB C
• Muscle, Smooth (drug effects, pathology)
• Ovalbumin (immunology)
• PPAR gamma (agonists, metabolism)
• Respiratory Hypersensitivity (drug therapy, physiopathology)
• Thiazolidinediones (administration & dosage, pharmacology, therapeutic use)
• Transforming Growth Factor beta1 (analysis, metabolism)
• Vascular Endothelial Growth Factor A (analysis, metabolism)