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

• Published in: International immunopharmacology Vol. 18; no. 2; pp. 311 - 324
• Main Authors: Kim, Seung-Hyung, Hong, Jung-hee, Lee, Young-Cheol
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2014
• Subjects: Allergens - immunology; Animals; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Asthma; 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; GATA-3; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - immunology; IL-17; Lung - immunology; Lung - pathology; Mice; Mice, Inbred BALB C; Neutrophils - immunology; Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology; Oleanolic acid; Oleanolic Acid - pharmacology; Oleanolic Acid - therapeutic use; Ovalbumin - immunology; Pneumonia - drug therapy; Pneumonia - immunology; Pneumonia - pathology; Pneumonia - physiopathology; RORγt; T-Box Domain Proteins - genetics; T-Box Domain Proteins - immunology; Th2; Th2 Cells - immunology; GATA-3; IL-17; Oleanolic acid; Asthma; Th2; RORγt
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.12.009

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. Proposed mechanisms of oleanolic acid in a mouse model of allergic asthma. [Display omitted] •Oleanolic acid suppressed of Th2 cytokines (IL-5, IL-13), B cell-dependent production of OVA-specific IgE.•Oleanolic acid suppressed eosinophil infiltration, allergic airway inflammation, and Penh.•Therapeutic effect of oleanolic acid is mediated by inhibition GATA-3, RORγt and Foxp3 pathways.