Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and Penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma.

Abstract

Allergic asthma is a chronic airway disorder characterized by airway hyperresponsiveness to allergens, chronic airway inflammation, airway edema, increased mucus secretion, excess production of Th2 cytokines, and eosinophil accumulation in the lungs. Ursolic acid is known for its pharmacological effects, such as its anti-tumor, anti-inflammatory and antimicrobial activities. To investigate the anti-asthmatic effects and mechanism of ursolic acid, we studied the development of pulmonary eosinophilic inflammation and enhanced pause (Penh) in a mouse model of allergic asthma. In this study, BALB/c mice were systemically sensitized to ovalbumin followed by intratracheal, intraperitoneal, and aerosol allergen challenges. We investigated the effect of ursolic acid and Cyclosporin A (CsA) on Penh, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokines, IL-17 production, and ovalbumin specific IgE production in a mouse model of asthma. In BALB/c mice, ursolic acid had suppressed eosinophil infiltration, allergic airway inflammation, and Penh, which occurred by suppressing the production of IL-5, IL-13, IL-17, and ovalbumin-specific IgE by blocking the GATA-3 and STAT6 pathways. Our data suggest the therapeutic mechanism of ursolic acid in asthma is based on reductions of Th2 cytokines (IL-5 and IL-13), ovalbumin-specific IgE production, and eosinophil infiltration via the Th2-GATA-3, STAT6, and IL-17-NF-κB pathways.

• Authors: Seung-Hyung Kim, Jung-Hee Hong, Young-Cheol Lee
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 701 Issue 1-3 Pg. 131-43 (Feb 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23201068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Asthmatic Agents
• Anti-Inflammatory Agents
• GATA3 Transcription Factor
• Gata3 protein, mouse
• Interleukin-13
• Interleukin-17
• Interleukin-5
• Interleukins
• PPAR gamma
• RNA, Messenger
• STAT6 Transcription Factor
• Triterpenes
• Immunoglobulin E
• Cyclosporine
• Ovalbumin
• ursolic acid

Topics

• Animals
• Anti-Asthmatic Agents (analysis, pharmacology, therapeutic use)
• Anti-Inflammatory Agents (analysis, pharmacology, therapeutic use)
• Asthma (complications, drug therapy)
• Bronchoalveolar Lavage Fluid (immunology)
• Cell Count
• Cell Line
• Cyclosporine
• Disease Models, Animal
• Down-Regulation (drug effects)
• Eosinophils (drug effects, immunology)
• Female
• GATA3 Transcription Factor (genetics)
• Hypersensitivity (complications)
• Immunoglobulin E (biosynthesis, blood)
• Inflammation (complications, drug therapy)
• Interleukin-13 (genetics)
• Interleukin-17 (genetics)
• Interleukin-5 (genetics)
• Interleukins (genetics)
• Lung (drug effects, immunology, metabolism, physiopathology)
• Macrophages (drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (adverse effects)
• PPAR gamma (agonists, genetics)
• RNA, Messenger (genetics, metabolism)
• STAT6 Transcription Factor (metabolism)
• Th2 Cells (drug effects, metabolism)
• Triterpenes (analysis, pharmacology, therapeutic use)