Esculetin Attenuates Th2 and Th17 Responses in an Ovalbumin-Induced Asthmatic Mouse Model

Inflammation. 2016 Apr;39(2):735-43. doi: 10.1007/s10753-015-0300-4.

Abstract

The purpose of the current study was to investigate the anti-asthmatic effect of esculetin (ES) and explore its potential mechanism with a mouse model of allergic asthma. A total number of 50 mice were randomly assigned to five groups: control, model, dexamethasone (Dex, 2 mg/kg), and ES (20 mg/kg, 40 mg/kg). Mouse asthma model was developed with the sensitization and challenge of ovalbumin (OVA). The levels of IgE in serum, eosinophilia infiltration, Th2/Th17 cytokines, Th17 cell frequency, histological condition, and the protein expressions of RORγt, GATA3 were detected. Our study demonstrated that ES inhibited, OVA-induced eosinophil count, interleukin-4 (IL-4), IL-5, IL-13, and IL-17A levels were recovered in bronchoalveolar lavage fluid. Flow cytometry (FCM) studies revealed that ES substantially inhibited Th17 cells' percentage. Western blot study also indicated that ES downregulated RORγt and GATA3 expressions. Meanwhile, ES had beneficial effects on the histological alteration. These findings suggested that ES might effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Keywords: GATA3; RORγt; Th17; Th2; asthma; esculetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Eosinophilia
  • Female
  • GATA3 Transcription Factor / biosynthesis
  • Immunoglobulin E / blood
  • Interleukin-13 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis
  • Ovalbumin
  • Random Allocation
  • Th17 Cells / immunology*
  • Th2 Cells / immunology*
  • Umbelliferones / therapeutic use*

Substances

  • Anti-Asthmatic Agents
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukin-13
  • Interleukin-17
  • Interleukin-5
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Umbelliferones
  • Interleukin-4
  • Immunoglobulin E
  • Dexamethasone
  • Ovalbumin
  • esculetin