Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factors T-bet, GATA-3, RORγt and Foxp3 in asthmatic mice

Int Immunopharmacol. 2014 Feb;18(2):311-24. doi: 10.1016/j.intimp.2013.12.009. Epub 2013 Dec 27.

Abstract

The natural product oleanolic acid is commonly found in a variety of medicinal plants. It is a triterpenoid compound known for its anti-inflammatory effects as well as various other pharmacological properties. The aim of the current study was to use a mouse model of allergic asthma to investigate whether oleanolic acid has anti-asthmatic effects, and if so, to determine the mechanism of these effects. Oleanolic acid 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 through the upregulation of T-bet and Foxp3, and the downregulation of GATA-3 and RORγt. The therapeutic effect of oleanolic acid was due to suppression of Th2 cytokines (IL-5 and IL-13), B cell-dependent production of OVA-specific IgE, and Gr-1 expression through the T-bet, GATA-3, retinoic acid-related orphan receptor γ t (RORγ t) and forkhead box p3 (Foxp3) transcription pathways. It is therefore reasonable to suggest that the anti-inflammatory and anti-asthmatic effects of oleanolic acid may be exerted through inhibition of the GATA-3 and RORγt pathways.

Keywords: Asthma; GATA-3; IL-17; Oleanolic acid; RORγt; Th2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / pathology
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Hyperreactivity / pathology
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / immunology
  • Eosinophils / immunology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Oleanolic Acid / pharmacology*
  • Oleanolic Acid / therapeutic use
  • Ovalbumin / immunology
  • Pneumonia / drug therapy
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Pneumonia / physiopathology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • Th2 Cells / immunology

Substances

  • Allergens
  • Anti-Asthmatic Agents
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Oleanolic Acid
  • Ovalbumin